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1.
Fitoterapia ; : 104352, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476400

RESUMO

Five new guaiane-type sesquiterpenoids were obtained from the roots of Daphne genkwa. Their gross structures were established by extensive spectroscopic analyses. Attempts on the assignment of the relative configurations were unsuccessful when based on the NOESY correlations. Therefore, NMR chemical shift calculations based on the gauge independent atomic orbital (GIAO) method in combination with the statistical method DP4+ were employed to establish their relative configurations. Furthermore, the absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism (ECD) using time-dependent density functional theory (TDDFT). The isolated compounds were screened for their cytotoxicity in vitro against two human hepatocellular carcinoma, HepG2 and Hep3B cell lines.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31478853

RESUMO

State-of-the-art neural style transfer methods have demonstrated amazing results by training feed-forward convolutional neural networks or using an iterative optimization strategy. The image representation used in these methods, which contains two components: style representation and content representation, is typically based on high-level features extracted from pretrained classification networks. Because the classification networks are originally designed for object recognition, the extracted features often focus on the central object and neglect other details. As a result, the style textures tend to scatter over the stylized outputs and disrupt the content structures. To address this issue, we present a novel image stylization method that involves an additional structure representation. Our structure representation, which considers two factors: i) the global structure represented by the depth map and ii) the local structure details represented by the image edges, effectively reflects the spatial distribution of all the components in an image as well as the structure of dominant objects respectively. Experimental results demonstrate that our method achieves an impressive visual effectiveness, which is particularly significant when processing images sensitive to structure distortion, e.g. images containing multiple objects potentially at different depths, or dominant objects with clear structures.

3.
Hum Mutat ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489982

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening (NBS) population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolour melting curve analysis (MMCA) to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top 5 frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and 4 pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were firstly reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities. This article is protected by copyright. All rights reserved.

4.
Plant Physiol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488573

RESUMO

Chloroplast size varies considerably in nature, but the underlying mechanisms are unknown. By exploiting a near-isogenic line population derived from a cross between the Arabidopsis (Arabidopsis thaliana) accessions Cape Verde Islands (Cvi-1), which has larger chloroplasts, and Landsberg erecta (Ler-0) with smaller chloroplasts, we determined that the large-chloroplast phenotype in Cvi-1 is associated with allelic variation in the gene encoding the chloroplast-division protein FtsZ2-2, a tubulin-related cytoskeletal component of the contractile FtsZ ring inside chloroplasts. Sequencing revealed that the Cvi-1 FtsZ2-2 allele encodes a C-terminally truncated protein lacking a region required for FtsZ2-2 interaction with inner envelope proteins, and functional complementation experiments in a Columbia-0 ftsZ2-2 null mutant confirmed this allele as causal for the increased chloroplast size in Cvi-1. Comparison of FtsZ2-2 coding sequences in the 1001 Genomes database showed that the Cvi-1 allele is rare and identified additional rare loss-of-function alleles, including a natural null allele, in three other accessions, all of which had enlarged-chloroplast phenotypes. The ratio of nonsynonymous to synonymous substitutions was higher among the FtsZ2-2 genes than among the two other FtsZ family members in Arabidopsis, FtsZ2-1, a close paralog of FtsZ2-2, and the functionally distinct FtsZ1-1, indicating more relaxed constraint on the FtsZ2-2 than FtsZ2-1 or FtsZ1-1 coding sequences. Our results establish that allelic variation in FtsZ2-2 contributes to natural variation in chloroplast size in Arabidopsis and also demonstrate that natural variation in Arabidopsis can be used to decipher the genetic basis of differences in fundamental cell biological traits, such as organelle size.

5.
Biosci Rep ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471533

RESUMO

Nucleus pulposus (NP) cell senescence is involved in disc degeneration. The in situ osmolarity within the NP region is an important regulator of disc cell's biology. However, its effects on NP cell senescence remain unclear. This study was aimed to investigate the effects and mechanism of hyper-osmolarity on NP cell senescence. Rat NP cells were cultured in the in situ-osmolarity medium and hyper-osmolarity medium. The reactive oxidative species (ROS) scavenger N-acetylcysteine (NAC) was added along with the medium to investigate the role of oxidative injury. Cell cycle, cell proliferation, senescence associated ß-galactosidase (SA-ß-Gal) activity, telomerase activity, expression of senescence markers (p16 and p53) and matrix molecules (aggrecan and collagen II) were tested to assess NP cell senescence. Compared with the in situ-osmolarity culture, hyper-osmolarity culture significantly decreased cell proliferation and telomerase activity, increased SA-ß-Gal activity and cell fraction in the G0/G1 phase, up-regulated expression of senescence markers (p16 and p53) and down-regulated expression of matrix molecules (aggrecan and collagen II), and increased intracellular ROS accumulation. However, addition of NAC partly reversed these effects of hyper-osmolarity culture on cellular senescence and decreased ROS content in NP cells. In conclusion, a hyper-osmolarity culture promotes NP cell senescence through inducing oxidative stress injury. This study provides new knowledge on NP cell senescence and helps us to better understand the mechanism of disc degeneration.

6.
Langmuir ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31474111

RESUMO

We demonstrated a novel nano-textured graphene micro-pad that can rapidly harvest water from the air to generate microscale water droplets with the desired size in designated positions on demand by simply applying a negative electric bias of -1.5 ~ -15V. More interestingly, the water droplets can be reversibly dried non-thermally with the pad at ambient temperature in humid air (~ 85%RH) by applying positive electric bias of +1.5 ~ +15V. The harvesting and drying rates on the glass are 2.7 m3/s and 1.5 m3/s under a bias of -15V and +15V, respectively, but no apparent harvesting or drying activities were observed without the bias. The energy consumption is minimal as there is no Joule current due to the insulative substrate. It was shown that substrate wettability and ions play an important role enabling the fast water harvesting and non-thermal drying. Molecular modeling is developed to understand the harvesting and drying mechanisms at the atomic scale. The water harvesting/drying approach may be useful for many technological applications such as micro-/nanolithography, 3D printing, MEMS, biochemical and microfluid devices.

7.
Can J Cardiol ; 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31474312

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis to assess the discrimination performance of the 2014 European Society of Cardiology (ESC) sudden cardiac death (SCD) risk-prediction model for hypertrophic cardiomyopathy (HCM). METHODS: We searched the PubMed, Embase and Web of Science, CNKI, WanFang, and China Biology Medicine disc (CBMdisc) databases for English and Chinese articles validating the risk model. The model's discrimination performance with cutoff points of 4% and 6% based on extracted information was calculated. The extracted C statistic and calculated area under the curve (AUC) with 95% confidence intervals (CIs) of all studies were weighted and summarized. Heterogeneity was quantified through I2 statistics; sensitivity analysis and publication bias were assessed with Egger's test. RESULTS: We included 13 studies validating the model's usefulness. We concluded that the model has excellent specificity, although it has poor sensitivity when setting a recommended cutoff value of 6% for identifying high-risk patients with HCM. In addition, there was moderate discrimination value (global C statistic = 0.75, 95% CI, 0.67-0.83; cutoff point of ≥ 4%; AUC = 0.69, 95% CI, 0.62-0.75; cutoff point of ≥ 6%; AUC = 0.65, 95% CI, 0.59-0.72). Subgroup analysis by region showed slightly weaker predictive ability for North America. There was no significant publication bias (all P > 0.05); sensitivity analysis did not change the results significantly. CONCLUSIONS: The 2014 ESC HCM SCD risk-prediction model has excellent specificity and poor sensitivity and has moderate discrimination performance. In addition, it may have lower prediction value for North America compared with other regions.

8.
J Hum Hypertens ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477828

RESUMO

Renal denervation (RDN) is a well-known innovative therapy for hypertension. However, the effects of global RDN on blood pressure (BP) lowering are quite variable. Insufficient and futile denervation is considered a major factor contributing to the variable results. Mapping renal nerves by renal nerve stimulation (RNS) is the most promising technique to improve the efficacy of RDN. We summarize the clinical and experimental data available regarding RNS-guided RDN and explain the roles of renal efferent nerves, afferent nerves and vagal nerves in BP changes. We further identify five different BP response patterns to RNS and provide an explanation of the underlying neuroanatomical basis.

9.
Complement Ther Clin Pract ; 36: 181-194, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383438

RESUMO

BACKGROUND AND PURPOSE: Vasomotor symptoms (VMS) are very common in menopausal populations and cancer patients and can cause physical and mental discomfort. We aim to summarize the findings of systematic reviews and meta-analyses (SRs/MAs) that assessed the effectiveness of complementary and alternative medicines(CAMs)on VMS to provide solid evidence for future practice. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to May 2019 to identify relevant SRs/MAs. The methodological quality of SRs/MAs and evidence levels of the outcomes were assessed. RESULTS: A total of 29 SRs/MAs were reviewed. Evidence has shown that acupuncture, hypnosis, paced respiration, cognitive behavioural therapy, genistein, soy isoflavones, S-equol, combined preparations of black cohosh, and omega-3 supplements could significantly reduce VMS. The methodological quality of the SRs/MAs was moderate or high. CONCLUSION: CAMs might be beneficial for reducing VMS, but the evidence levels were not high. Several priorities for future practice were identified.

10.
Cancer Sci ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385398

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of ß-catenin by dephosphorylating ß-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by ß-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating ß-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.

11.
BMC Med Genomics ; 12(1): 124, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443660

RESUMO

BACKGROUND: Non-coding RNA has been shown to participate in numerous biological and pathological processes and has attracted increasing attention in recent years. Recent studies have demonstrated that long non-coding RNA and micro RNA can interact through various mechanisms to regulate mRNA. Yet the gene-gene interaction has not been investigated in coronary heart disease (CHD). METHODS: High throughput sequencing were used to identify differentially expressed (DE) lncRNA, miRNA, and mRNA profiles between CHD and healthy control. Gene Oncology (GO), KEGG enrichment analysis were performed. Gene-gene interaction network were constructed and pivotal genes were screened out. Lentivirus-induced shRNA infection and qRT-PCR were performed to validated the gene-gene interactions. RESULTS: A total of 62 lncRNAs, 332 miRNAs and 366 mRNAs were differentially expressed between CHD and healthy control. GO and KEGG analysis show that immune related molecular mechanisms and biological processes play a role in CHD. The gene-gene interaction network were constructed and visualized based on Pearson correlation coefficients and starBase database. 6 miRNAs in the network were significantly correlated to left ventricular ejection fraction, total choleterol and homocysteine. 2 lncRNAs (CTA-384D8.35 and CTB-114C7.4 (refseq entry LOC100128059)), 1 miRNA (miR-4497), and 1 mRNA (NR4A1) were the pivotal genes. Lentivirus-induced shRNA infection and qRT-PCR had validated the pivotal gene-gene interactions. CONCLUSIONS: These results have shown the potential of lncRNA, miRNA, and mRNA as clinical biomarkers and in elucidating pathological mechanisms of CHD from a transcriptomic perspective.

12.
Bioorg Med Chem ; 27(18): 4089-4100, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31378597

RESUMO

Aiming to develop potent JAK inhibitors, two series of 4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives (8a-8p and 11a-11i) were designed and synthesized by coalescing various N-acylpiperidine motifs with baricitinib. The pharmacological results based on enzymatic and cellular assays identified the optimized compound 11e, which exerted over 90% inhibition rates against JAK1 and JAK2, and displayed the most compelling anti-inflammatory efficacy superior to baricitinib by inhibiting NO generation from LPS-induced RAW264.7 macrophages. Importantly, low cytotoxity of 11e was revealed by the IC50 value of 88.2 µM against normal RAW264.7 cells. The binding mode of 11e with JAK1 and JAK2 identified the essential structural bases in accord with SARs analysis. Furthermore, cellular morphology observation and western blot analysis disclosed the ability of 11e to relieve cells inflammatory damage by significantly down-regulating LPS-induced high expression of JAK1, JAK2, as well as pro cytokine IL-1ß. Together, 11e was verified as a promising lead for JAK inhibitors for the treatment of inflammatory diseases.

13.
Lung Cancer ; 135: 116-122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31446983

RESUMO

OBJECTIVES: The utility of malignant pleural effusion (MPE) as a source for determining EGFR mutations to guide EGFR TKI therapy in advanced adenocarcinoma of the lung remains unclear. This study compared MPE, plasma and tumor tissues as sources of biological samples for EFGR mutational analysis of lung adenocarcinoma patients. MATERIALS AND METHODS: Total 295 MPE samples were retrospectively collected from lung adenocarcinoma patients. Matched tissue and plasma samples were available for 92 patients, and 248 patients had plasma samples. EGFR exon-19-deletion and exon 21-L858R mutation were detected with Denaturing high performance liquid chromatography (DHPLC). The concordance of EGFR mutation status in MPE, tissue, and plasma were evaluated, and the value of EGFR mutations in MPE with respect to efficacy of EGFR-TKI was investigated. RESULTS: The EGFR mutation rate in MPE samples was 39.3% (116/295). The concordance between MPEs and tissues was 87.1% (Kappa = 0.71); the sensitivity and specificity of EGFR mutation in MPEs according to tissues was 71.4% and 96.5%, respectively. And 219 patients received EGFR-TKI, and the objective response rate was similar for patients with EGFR mutation either in MPE, tissues or plasma (57.6% vs 56.0% vs 47.4%, p = 0.51). Similar results were found in progression free survival (8.9 months vs 9.0 months vs 7.7 months, p = 0.077 and overall survival (29.8 months vs 25.9 months vs 25.3 months, p = 0.33). CONCLUSION: MPE is a reliable surrogate for tumor tissue for identifyingEGFR mutations. MPE could offer reference of EGFR mutation to EGFR-TKIs treatment decision for advanced lung adenocarcinoma patients even when tissue and plasma were available.

14.
Food Chem ; 301: 125224, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31374530

RESUMO

This study was the first investigation into the main inducers of two lignifications by examining the changes of physicochemical properties and gene expression in king oyster mushrooms, under different conditions, during 21 days of storage. The results showed that the toughness, firmness and gumminess of the no-wounding treatment decreased to approximately 75-82.5% of the initial values, and the lignin content and expression of Pe4CL1 and Pe4CL3 decreased by 21-40% and 22-77%, respectively, in comparison to those of the other treatments in the first lignification. These findings indicated that wounding was the main factor inducing the first lignification. The second lignification of tested mushrooms was positively correlated with reactive oxygen species (ROS)-mediated senescence, accompanied by increased malondialdehyde (MDA) content, electrolyte leakage rate and mitochondrial dysfunction, which showed that ROS-mediated senescence played an essential role in the second lignification. This study is helpful for effective strategies to reduce lignification in stored mushrooms.

15.
Neurosci Bull ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444652

RESUMO

Efficient viral vectors for mapping and manipulating long-projection neuronal circuits are crucial in structural and functional studies of the brain. The SAD strain rabies virus with the glycoprotein gene deleted pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows strong neuro-tropism in cell culture, but its in vivo efficiency for retrograde gene transduction and neuro-tropism have not been systematically characterized. We compared these features in different mouse brain regions for SAD-RV-N2C(G) and two other widely-used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro. We found that SAD-RV(ΔG)-N2C(G) enhanced the infection efficiency of long-projecting neurons by ~10 times but with very similar neuro-tropism, compared with SAD-RV(ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) had an infection efficiency comparable with rAAV2-retro, but a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1227-1231, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418384

RESUMO

OBJECTIVE: To investigate the genetic carrier rate of thalassemia and its gene mutation types as well as the distribution characteristics among the people in Lingshui Li autonomous county of Hainan province, so as to provide the basis for making the prevention programs of thalassemia in administrative departments. METHODS: Samples were collected from couples undergoing premarital and pregestational screenings, in which the positive ones in preliminary screening were further tested by genetic diagnoses and the genotypes were analyzed. RESULTS: The rate of thalassemia gene carriers was 19.41% (274/1412) of the couples of childbearing age in Lingshui Li autonomous County of Hainan Province. In these carriers,α-thalassemia accounted for 83.21%(228/274), ß-thalassemia for 8.03%(22/274), and both α-and ß-thalassemia gene accounted for 8.76% (28/274). CONCLUSION: The carrying rate of thalassemia gene in population Lingshui Li autonomous county of Hainan province is high, and its distribution has geographical characteristics,the major type is α-thalassemia. Blood screening and genetic diagnosis of thalassemia should be strengthened, and corresponding measures should be taken to reduce its gene frequency.


Assuntos
Talassemia alfa , Talassemia beta , China , Testes Genéticos , Genótipo , Heterozigoto , Humanos
17.
J Cell Biochem ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452262

RESUMO

The oncogenesis and progression of gastric cancer are closely correlated with the complex regulatory relationships among messenger RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA). After constructing the gastric cancer lncRNA-miRNA-mRNA regulatory network, we analyzed the network topology properties and found that lncRNA ADAMTS9-AS2 and C20orf166-AS1 and miRNA hsa-mir-204 are key nodes. Further functional enrichment analysis and survival analysis were performed on these key nodes and the RNAs interacting with them. We found that CHRM2, ANGPT2, and COL1A1 interacting with ADAMTS9-AS2 are enriched in the PI3K-Akt signaling pathway, and low expression of the ADAMTS9-AS2 is closely related to the prognosis of patients. Abnormal expression of CACNA1H, FLNA, and FLNC interacting with lncRNA C20orf166-AS1 is associated with MAPK signaling pathway in gastric cancer. In addition, the downregulated miRNA hsa-mir-204 promotes invasion and proliferation of gastric cancer cells by regulating the abnormal expression of mRNAs (CHRDL1 and NPTX1) and lncRNAs (ADAMTS9-AS2, NKX2-1-AS1, TLR8-AS1, and VCAN-AS1). This study systematically analyzed the lncRNA-miRNA-mRNA regulatory network of gastric cancer, which not only has a new understanding of the pathogenesis of gastric cancer, but also provides new insights for the early diagnosis and treatment of gastric cancer.

18.
J Clin Lab Anal ; : e23006, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420923

RESUMO

BACKGROUND: This study aimed to assess the correlation of circulating microRNA-103 (miR-103) and microRNA-107 (miR-107) with disease risk and cognitive impairment of Alzheimer's disease (AD). METHODS: Plasma samples from 120 AD patients, 120 Parkinson's disease (PD) patients (served as disease control), and 120 healthy controls were collected for miR-103 and miR-107 detections using real-time quantitative polymerase chain reaction. Mini-Mental State Examination (MMSE) score was documented and was used to accordingly assess the dementia severity. RESULTS: miR-103 expression was decreased in AD patients compared with PD patients and healthy controls, and receiver operating characteristic (ROC) curve analyses illustrated that it was able to differentiate AD patients from PD patients and healthy controls. Additionally, miR-103 positively correlated with MMSE score and negatively correlated with dementia severity in AD patients. miR-107 expression was lower in AD patients compared with healthy controls but similar between AD patients and PD patients, and ROC curve analyses revealed that it was able to differentiate AD patients from healthy controls but not AD patients from PD patients. miR-107 was positively correlated with MMSE score and negatively correlated with dementia severity in AD patients, while the correlation coefficient of miR-107 with MMSE score was lower than that of miR-103 with MMSE score. Besides, miR-103 was positively correlated with miR-107 in AD patients, PD patients, and healthy controls. CONCLUSION: miR-103 may be a better choice than miR-107 to serve as a potential biomarker for disease risk and disease progression of AD.

19.
PLoS Pathog ; 15(8): e1007703, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31381590

RESUMO

Necrotrophic plant pathogens acquire nutrients from dead plant cells, which requires the disintegration of the plant cell wall and tissue structures by the pathogen. Infected plants lose tissue integrity and functional immunity as a result, exposing the nutrient rich, decayed tissues to the environment. One challenge for the necrotrophs to successfully cause secondary infection (infection spread from an initially infected plant to the nearby uninfected plants) is to effectively utilize nutrients released from hosts towards building up a large population before other saprophytes come. In this study, we observed that the necrotrophic pathogen Dickeya dadantii exhibited heterogeneity in bacterial cell length in an isogenic population during infection of potato tuber. While some cells were regular rod-shape (<10µm), the rest elongated into filamentous cells (>10µm). Short cells tended to occur at the interface of healthy and diseased tissues, during the early stage of infection when active attacking and killing is occurring, while filamentous cells tended to form at a later stage of infection. Short cells expressed all necessary virulence factors and motility, whereas filamentous cells did not engage in virulence, were non-mobile and more sensitive to environmental stress. However, compared to the short cells, the filamentous cells displayed upregulated metabolic genes and increased growth, which may benefit the pathogens to build up a large population necessary for the secondary infection. The segregation of the two subpopulations was dependent on differential production of the alarmone guanosine tetraphosphate (ppGpp). When exposed to fresh tuber tissues or freestanding water, filamentous cells quickly transformed to short virulent cells. The pathogen adaptation of cell length heterogeneity identified in this study presents a model for how some necrotrophs balance virulence and vegetative growth to maximize fitness during infection.

20.
PLoS One ; 14(8): e0220143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415580

RESUMO

PURPOSE: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

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