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1.
Sci Rep ; 10(1): 16308, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004874

RESUMO

Genotyping-by-Sequencing (GBS) is a low-cost, high-throughput genotyping method that relies on restriction enzymes to reduce genome complexity. GBS is being widely used for various genetic and breeding applications. In the present study, 2240 individuals from eight maize populations, including two association populations (AM), backcross first generation (BC1), BC1F2, F2, double haploid (DH), intermated B73 × Mo17 (IBM), and a recombinant inbred line (RIL) population, were genotyped using GBS. A total of 955,120 of raw data for SNPs was obtained for each individual, with an average genotyping error of 0.70%. The rate of missing genotypic data for these SNPs was related to the level of multiplex sequencing: ~ 25% missing data for 96-plex and ~ 55% for 384-plex. Imputation can greatly reduce the rate of missing genotypes to 12.65% and 3.72% for AM populations and bi-parental populations, respectively, although it increases total genotyping error. For analysis of genetic diversity and linkage mapping, unimputed data with a low rate of genotyping error is beneficial, whereas, for association mapping, imputed data would result in higher marker density and would improve map resolution. Because imputation does not influence the prediction accuracy, both unimputed and imputed data can be used for genomic prediction. In summary, GBS is a versatile and efficient SNP discovery approach for homozygous materials and can be effectively applied for various purposes in maize genetics and breeding.

2.
Mol Med Rep ; 22(5): 4031-4040, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000215

RESUMO

Histone deacetylase 4 (HDAC4) plays a vital role in chondrocyte hypertrophy and bone formation. To investigate the function of HDAC4 in postnatal skeletal development, the present study developed lineage­specific HDAC4­knockout mice [collagen type 2α1 (Col2α1)­Cre, HDAC4d/d mice] by crossing transgenic mice expressing Cre recombinase. Thus, a specific ablation of HDAC4 was performed in Col2α1­expressing mice cells. The knee joints of HDAC4fl/fl and Col2α1­Cre, HDAC4d/d mice were analyzed at postnatal day (P)2­P21 using an in vivo bromodeoxyuridine (BrdU) assay, and Safranin O, Von Kossa and whole­body staining were used to evaluate the developmental growth plate, hypertrophic differentiation, mineralization and skeletal mineralization patterns. The trabecular bone was analyzed using microcomputed tomography. The expressions of BrdU, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)­13, runt­related transcription factor (Runx)­2, osteoprotegerin (OPG), CD34, type X collagen (ColX), osteocalcin and Wnt5a were determined using immunohistochemistry, in situ hybridization (ISH) and reverse transcription­quantitative (RT­q)PCR. The results demonstrated that HDAC4­null mice (HDAC4d/d mice) were severely runted; these mice had a shortened hypertrophic zone (histopathological evaluation), accelerated vascular invasion and articular mineralization (Von Kossa staining), elevated expressions of MMP­13, Runx2, OPG and CD34 (RT­qPCR and immunohistochemistry), downregulated expression of the proliferative marker BrdU and PCNA (immunohistochemistry), increased expression of ColX and decreased expression of Wnt5a (ISH). In conclusion, chondrocyte­derived HDAC4 was responsible for regulating chondrocyte proliferation and differentiation as well as endochondral bone formation.

3.
J Nanobiotechnology ; 18(1): 142, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008457

RESUMO

This review focuses on the recent advances in the synthesis of graphene quantum dots (GQDs) and their applications in drug delivery. To give a brief understanding about the preparation of GQDs, recent advances in methods of GQDs synthesis are first presented. Afterwards, various drug delivery-release modes of GQDs-based drug delivery systems such as EPR-pH delivery-release mode, ligand-pH delivery-release mode, EPR-Photothermal delivery-Release mode, and Core/Shell-photothermal/magnetic thermal delivery-release mode are reviewed. Finally, the current challenges and the prospective application of GQDs in drug delivery are discussed.

4.
Ocul Immunol Inflamm ; : 1-6, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021424

RESUMO

PURPOSE: To investigate the clinical settings and features, management, and visual outcomes of exogenous bacterial endophthalmitis with retinal vasculitis and posterior pole preretinal exudates. METHODS: Retrospectively reviewed records for 40 eyes of 40 patients. RESULTS: Retinal vasculitis was identified with focal type in eight eyes and diffuse type in 32 eyes. Posterior pole preretinal exudates were identified with discrete type in 23 eyes and condensed type in 17 eyes. Final VA was 20/200 or better in 23 of 40 eyes (57.5%). Multivariate linear regression revealed that condensed posterior pole preretinal exudates (P =.005) and ocular hypertension (P =.012) were the significant independent factors for poor visual outcomes. CONCLUSIONS: Condensed posterior pole preretinal exudates and ocular hypertension are critical prognostic factors for poor visual outcomes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33067168

RESUMO

BACKGROUND AND AIM: Post-hepatectomy liver failure (PHLF) remains the primary cause of in-hospital mortality after hepatectomy. Identifying predictors of PHLF is important to improve surgical safety. We sought to identify the predictive accuracy of two noninvasive markers, albumin-bilirubin (ALBI) and aspartate aminotransferase to platelet count ratio index (APRI), to predict PHLF among patients with hepatocellular carcinoma (HCC), and to build up an online prediction calculator. METHODS: Patients who underwent resection for HCC between 2013 and 2016 at 6 Chinese hospitals were retrospectively analyzed. The independent predictors of PHLF were identified using univariate and multivariate analyses; derivative data were used to construct preoperative and postoperative nomogram models. Receiver operating characteristic (ROC) curves for the two predictive models, and ALBI, APRI, Child-Pugh, model for end-stage liver disease (MELD) scores were compared relative to predictive accuracy for PHLF. RESULTS: Among the 767 patients in the analytic cohort, 102 (13.3%) experienced PHLF. Multivariable logistic regression analysis identified high ALBI grade (>-2.6) and high APRI grade (>1.5) as independent risk factors associated with PHLF in both the preoperative and postoperative models. Two nomogram predictive models and corresponding web-based calculators were subsequently constructed. The areas under the ROC curves for the postoperative and preoperative models, APRI, ALBI, MELD and Child-Pugh scores in predicting PHLF were 0.844, 0.789, 0.626, 0.609, 0.569, and 0.560, respectively. CONCLUSIONS: ALBI and APRI demonstrated more accurate ability to predict PHLF than Child-Pugh and MELD. Two online calculators that combined ALBI and APRI were proposed as useful preoperative and postoperative tools for individually predicting the occurrence of PHLF among patients with HCC.

6.
Cell Death Dis ; 11(10): 864, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060569

RESUMO

Metastasis is the main cause of laryngeal cancer-related death; its molecular mechanism remains unknown. Here we identify protein arginine methyltransferase 5 (PRMT5) as a new metastasis-promoting factor in laryngeal carcinoma, and explore its underlying mechanism of action in regulating laryngeal cancer progression. We illustrated that PRMT5 expression was positively correlated with tumor stages, lymphatic metastasis, and unfavorable outcome. Functional assays revealed that PRMT5 promoted laryngeal carcinoma cell proliferation, migration, and invasive capacity in vitro, as well as lymph-node metastasis in vivo. The ectopic expression of PRMT5 induced EMT with downregulation of E-cadherin and upregulation of N-cadherin, snail, and MMP9. Mechanistic results revealed that the metastatic effects could be attributed to PRMT5-mediated activation of Wnt signaling, and Wnt4 is an important driver of Wnt/ß-catenin signaling pathway. Wnt4 silencing could reverse PRMT5-induced cell proliferation, migration, and invasion capacities. Furthermore, inhibition of the Wnt/ß-catenin signaling pathway abolished the effect of PRMT5-induced proliferation, whereas activation of the pathway enhanced the effect of PRMT5 overexpression on cell proliferation. These results demonstrated that the oncogenic role of PRMT5 could be attributed to PRMT5/Wnt4 axis-mediated activation of the Wnt/ß-catenin signaling pathway. PRMT5 may serve as a novel prognostic marker and a therapeutic target for lymphatic metastasis of laryngeal carcinoma.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33079978

RESUMO

Arterial marker genes EphrinB2 and HEY2 are essential for cardiovascular development and postnatal neovascularization. Our previous study confirmed that E2F1 could activate the transcription of EphrinB2 and HEY2 in human mesenchymal stem cells; however, the detailed mechanism has not been resolved yet. In this study, we focused on the interaction between E2F1 and DNMT3A, a de novo DNA methyltransferase, on regulating the expression of EphrinB2 and HEY2, and explored the potential mechanisms. Gain- and loss-of-function experiments implicated the positive effect of E2F1 on the expression of EphrinB2 and HEY2 and tube formation in human umbilical artery endothelial cells. Accumulation of DNMT3A decreased the levels of EphrinB2 and HEY2, and impaired tube formation induced by E2F1, while inhibiting DNMT3A by RNA interference augmented their expression and angiogenesis in E2F1-trasfected cells. We then asked whether the low expressions of EphrinB2 and HEY2 induced by DNMT3A are related to the methylation status of their promoters. Surprisingly, the methylation status of the CpG islands in the promoter region was not significantly affected by overexpression of exogenous DNMT3A. Furthermore, the interaction between E2F1 and DNMT3A was confirmed by co-immunoprecipitation. DNMT3A could inhibit the transcription of EphrinB2 and HEY2 promoters by affecting the binding of E2F1 to its recognition sequences as revealed by luciferase reporter assay and chromatin immunoprecipitation. These results identified a novel mechanism underlying the cooperation of DNMT3A with E2F1 on regulating target gene expression, and revealed their roles in the angiogenic process.

8.
Protein Sci ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007128

RESUMO

Human ATP-binding cassette transporter 6 of subfamily B (ABCB6) is an ABC transporter involved in the translocation toxic metals and anti-cancer drugs. Using cryo-electron microscopy, we determined the molecular structure of full-length ABCB6 in an apo state. The structure of ABCB6 unravels the architecture of a full-length ABCB transporter that harbors two N-terminal transmembrane domains which is indispensable for its ATPase activity in our in vitro assay. A slit-like substrate binding pocket of ABCB6 may accommodate the planar shape of porphyrins, and the existence of a secondary cavity near the mitochondrial intermembrane space side would further facilitate substrate release. Furthermore, the ATPase activity of ABCB6 stimulated with a variety of porphyrin substrates showed different profiles in the presence of glutathione (GSH), suggesting the action of a distinct substrate translocation mechanism depending on the use of GSH as a cofactor.

9.
J Clin Neurosci ; 79: 54-59, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070918

RESUMO

PURPOSE: Facetectomy is a useful procedure in percutaneous transforaminal endoscopic discectomy (PTED) for the enlargement of surgical field and operative space and for the decompression of existing nerve roots for patients who suffer foraminal stenosis. Biomechanical deterioration can initially trigger the adjacent segment disease (ASD), and our previous literature proved that a large grade of facetectomy can increase the risk of biomechanical deterioration and resulting low back pain. However, no study has discussed whether different grades of facetectomy influence the risk of ASD. METHODS: A validated osteoligamentous lumbosacral finite element model and corresponding PTED models with quarter and half facetectomy were constructed in our previous study. Biomechanical indicators were computed and recorded to evaluate the risk of ASD. RESULTS: Obvious differences between the intact model and the quarter facetectomy model had no basis. Nevertheless, in most body positions, most of the above indicators deteriorated in the half facetectomy model. CONCLUSION: On the basis of achieving the surgical purpose in PTED, the superior articular process should be protected to decrease the risk of ASD biomechanically.

10.
J Med Virol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073361

RESUMO

Hyperglycemia commonly occurred in severe cases with COVID-19. In this study, we explored the associations between admission fasting plasma glucose (FPG) and 28-day mortality in COVID-19 patients. In this single centre retrospective study, 263 adult patients with COVID-19 were included. Demographic and clinical information were collected and compared between patients with and without diabetes. Cox regression analyses was used to investigate the risk factors of 28-day mortality in hospital. Of 263 patients, 161 (61.2%) were male, 62 (25.6%) had a known history of diabetes, and 135 (51.3%) experienced elevated FPG (> 7.0 mmol/L) at hospital admission. The median FPG in patients with diabetes was much higher than in patients without diabetes (12.79 mmol/L versus 6.47 mmol/L). Patients with diabetes had higher neutrophil count and D-dimer, less lymphocyte count, lower albumin level, and more fatal complications. Multivariable Cox regression analyses showed that age (per 10-year increase) (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.13-1.74), admission FPG between 7.0 and 11.0 mmol/L and ≥11.1 mmol/L (HR, 1.90, 95% CI, 1.11-3.25; HR, 2.09, 95% CI, 1.21-3.64, respectively), chronic obstructive pulmonary disease (HR, 2.89, 95% CI, 1.31-6.39), and cardiac injury (HR, 2.14; 95% CI, 1.33-3.47) were independent predictors of 28-day mortality in COVID-19 patients. Hyperglycemia on admission predicted worse outcome in hospitalized patients with COVID-19. Intensive monitoring and optimal glycemic control may improve the prognosis of COVID-19 patients. This article is protected by copyright. All rights reserved.

11.
Int J Mol Sci ; 21(19)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33027889

RESUMO

Cx43 hemichannels (HCs) are electrically and chemically gated transmembrane pores with low open probability and multiple conductance states, which makes kinetic studies of channel gating in large datasets challenging. Here, we developed open access software, named HemiGUI, to analyze HC gating transitions and investigated voltage-induced HC opening based on up to ≈4000 events recorded in HeLa-Cx43-overexpressing cells. We performed a detailed characterization of Cx43 HC gating profiles and specifically focused on the role of the C-terminal tail (CT) domain by recording the impact of adding an EGFP tag to the Cx43 CT end (Cx43-EGFP) or by supplying the Cx43 HC-inhibiting peptide Gap19 that interferes with CT interaction with the cytoplasmic loop (CL). We found that Gap19 not only decreased HC opening activity to the open state (≈217 pS) but also increased the propensity of subconductance (≈80 pS) transitions that additionally became slower as compared to the control. The work demonstrates that large sample transition analysis allows detailed investigations on Cx43 HC gating and shows that Gap19 acts as a HC gating modifier by interacting with the CT that forms a crucial gating element.

12.
Sci Total Environ ; 754: 141812, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32906035

RESUMO

To explore the photochemical O3 pollution over the Pearl River Estuary (PRE), intensive measurements of O3 and its precursors, including trace gases and volatile organic compounds (VOCs), were simultaneously conducted at a suburban site on the east bank of PRE (Tung Chung, TC) in Hong Kong and a rural site on the west bank (Qi'ao, QA) in Zhuhai, Guangdong in autumn 2016. Throughout the sampling period, 3 days with high O3 levels (maximum hourly O3 > 100 ppbv) were captured at both sites (pattern 1) and 13 days with O3 episodes occurred only at QA (pattern 2). It was found that O3 formation at TC was VOC-limited in both patterns because of the large local NOx emissions. However, the O3 formation at QA was co-limited by VOCs and NOx in pattern 1, but VOC-limited in pattern 2. In both patterns, isoprene, formaldehyde, xylenes and trimethylbenzenes were the top 4 VOCs that modulated local O3 formation at QA, while they were isoprene, formaldehyde, xylenes and toluene at TC. In pattern 1, the net O3 production rate at QA (13.1 ± 1.6 ppbv h-1) was high, and comparable (p = 0.40) to that at TC (12.1 ± 1.5 ppbv h-1), so was the hydroxyl radical (i.e., OH), implying high atmospheric oxidative capacity over PRE. In contrast, the net O3 production rate was significantly higher (p < 0.05) at QA (16.3 ± 0.4 ppbv h-1) than that at TC (4.7 ± 0.2 ppbv h-1) in pattern 2, and the OH concentration and cycling rate were also higher, indicating much stronger photochemical reactions at QA. These findings enhanced our understanding of O3 photochemistry in the Pearl River estuary, which could be extended to other estuaries.

13.
Talanta ; 220: 121352, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928390

RESUMO

Metal-organic framework materials (MOFs) are highly promising materials for biomedical applications owing to high porosity, adjustable pore structure and high loading capacity. In this paper, we herein reported a novel UiO-66-NH2 MOF-based ratiometric fluorescent probe for the high sensitive detection of dopamine and reduced glutathione. Light-emitting metal-organic framework materials UiO-66-NH2 MOF with a fluorescence emission wavelength of 450 nm was synthesized by a simple hydrothermal synthesis. Dopamine could self-oxidize in polyethyleneimine (PEI) solution to form copolymer (PDA-PEI), which can emit yellow-green fluorescence at 530 nm. PDA-PEI can quench the fluorescence of UiO-66-NH2 MOF via FRET and the fluorescence intensity of PDA-PEI at 530 nm is increasing. Due to the reductive properties of glutathione, the formation of PDA-PEI could be blocked and the fluorescence of the UiO-66-NH2 MOF could be restored. Therefore, dopamine and reduced glutathione could be detected simultaneously via monitoring the ratiometric fluorescence intensity (I530/I450). The ratiometric fluorescent method showed good linearity curve with the concentration of dopamine in the range of 4-50 µM and with the concentration of reduced glutathione in the range of 1-70 µM. Furthermore, the ratiometric fluorescent method had a low detection limit for DA (0.68 µM) and GSH (0.57 µM), and was successfully applied for DA and GSH determination in human serum.

14.
Int J Med Sci ; 17(15): 2276-2284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922192

RESUMO

Purpose: The present study focused on the long-term prognostic value of dynamic body mass index (BMI) change in gastric cancer patients who underwent gastrectomy. Methods: Clinical data from a total of 576 gastric cancer patients who underwent radical gastrectomy were collected. Univariate and multivariate analyses were performed to demonstrate the association between dynamic BMI variables (BMI before surgery, 1 month, 6 months or 12 months after surgery) and prognosis (DFS and OS). The correlation between BMI loss after surgery and survival outcomes was also evaluated. Results: Post-operative BMI, especially BMI at one year after surgery (p<0.001), was an independent risk factor of recurrence and mortality, wherein patients with high-BMI (≥23) showed significantly better outcomes than patients with normal-BMI (18.5-23) (DFS, HR:0.49; 95% CI:0.31-0.78; OS, HR:0.30; 95% CI: 0.15-0.59). On the contrary, low-BMI (<18.5) patients presented with worse outcomes (DFS, HR: 1.34; 95% CI: 1.00-1.80; OS, HR: 1.68; 95% CI: 1.20-2.34). In addition, compared with moderate BMI loss (≤10%), severe postoperative BMI loss (>10%) at one year was independently associated with substantially worse prognosis for DFS (HR: 1.54; 95% CI: 1.15-2.08) and OS (HR: 1.45; 95% CI: 1.02-2.06). Subgroup analysis indicated that gender (p=0.03), extent of resection (p<0.001), tumor site (p=0.001) and perineural invasion (p=0.007) were associated with postoperative BMI loss at one year. The prognostic value of postoperative BMI loss at one year was consistent among most clinicopathological subgroups, except for tumor site (interaction p=0.025 for OS). Conclusion: In Chinese gastric cancer patients who underwent gastrectomy, higher postoperative BMI (≥ 23) was significantly associated with longer survival time, whereas severe BMI loss (>10%) at one year after surgery was associated with worse outcomes. Thus, body weight maintenance after treatment is important, and dynamic monitoring of body weight and nutritional status should be emphasized in clinical practice.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32880058

RESUMO

Heat shock protein 60 (HSP60) is a well-recognized multifunctional protein, playing a substantial role in protecting organisms from environmental stress. The domestic pigeon (Columba livia) is a promising model organism, with important economic and ecological value, and its health is susceptible to temperature stress. To explore the molecular characteristics, tissue expression profile, and response to temperature stress for HSP60 of Columba livia (ClHSP60), we firstly cloned and characterized the complete cDNA sequence and investigated its expression profile under optimal conditions and acute temperature stress. The cDNA of ClHSP60 contained 2257 nucleotides, consisting of 12 exons with length ranging from 65 to 590 bp. The open reading frame (ORF) encoded 573 amino acids with calculated molecular weight of 60.97 kDa that contained a number of structurally prominent domains or motifs. Under optimal temperature conditions, levels of ClHSP60 expression differed between all the tested tissues (the highest was noted in liver and the lowest in pectoralis major muscle). Under acute temperature stress, five patterns of change were detected in the tested tissues, suggesting that different tissues in domestic pigeons differentially responded to various temperature stress conditions. Upregulation of ClHSP60 expression was highest in the lung and pectoralis major muscle, reflecting the crucial role of these two tissues in temperature regulation. However, the crop, cerebrum, and heart showed little change or decreased ClHSP60 expression. The results indicate that ClHSP60 may be sensitive to and play pivotal roles in responding to acute temperature stress.

16.
Aging (Albany NY) ; 12(18): 18415-18435, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991322

RESUMO

The association between vitamin C intake and breast cancer is unclear. This meta-analysis aimed to precisely assess the association of vitamin C intake with breast cancer risk and mortality. We searched the PubMed, Embase, and Web of Science databases up to June 2020 and found 69 studies relevant to breast cancer risk (54 studies) and survival (15 studies). Relative risks and 95% confidence intervals were calculated using the random-effects models. Pooled results suggested that the highest versus lowest vitamin C intake was significantly associated with a lower risk of breast cancer incidence (Relative Risk = 0.86; 95% confidence interval, 0.81-0.92). Dietary vitamin C but not supplements was found to reduce breast cancer risk (Relative Risk = 0.89; 95% confidence interval, 0.82-0.96). For the highest versus lowest vitamin C intake, the pooled hazard risk for breast cancer-specific mortality was 0.78 (95% confidence interval, 0.69-0.88), totality mortality was 0.82 (95% confidence interval, 0.74-0.91), and recurrence was 0.81 (95% confidence interval, 0.67-0.99). Our analysis suggests that higher vitamin C intake is significantly associated with reduced breast cancer incidence and mortality. However, the intake of vitamin C supplements has no significant effect on breast cancer prevention.

17.
Eur Phys J E Soft Matter ; 43(9): 57, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920678

RESUMO

The rich island morphology of two-dimensional (2D) materials during chemical vapor deposition (CVD) growth process is studied using a computational model based on a Burton-Cabrera-Frank (BCF) type crystal growth theory. A previously formulated phase-field (PF) model for the BCF crystal growth process is employed to investigate the effect of various growth conditions, such as the concentration of absorbed atoms on the substrate and the growth temperature, that have been experimentally known to significantly impact the island morphology. It is shown that, within this simple model, the rich morphology of 2D islands in CVD growth can be well reproduced. With increasing substrate temperature, the 2D island changes from dendritic to compact shape. When considering the energy difference between the zigzag and the armchair edges of the 2D island, most commonly known morphologies, from quasi-sixfold compact islands to spiky triangular and compact triangular shapes, are observed in the model. Growth mechanisms associated with different island shapes and potential model improvements are also discussed.

18.
Adv Biosyst ; : e2000134, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32924336

RESUMO

Hair-follicle-derived stem cells (HSCs) originating from the bulge region of the mouse vibrissa hair follicle are able to differentiate into neuronal and glial lineage cells. The tropomyosin receptor kinase A (TrkA) receptor that is expressed on these cells plays key roles in mediating the survival and differentiation of neural progenitors as well as in the regulation of the growth and regeneration of different neural systems. In this study, the OptoTrkA system is introduced, which is able to stimulate TrkA activity via blue-light illumination in HSCs. This allows to determine whether TrkA signaling is capable of influencing the proliferation, migration, and neural differentiation of these somatic stem cells. It is found that OptoTrkA is able to activate downstream molecules such as ERK and AKT with blue-light illumination, and subsequently able to terminate this kinase activity in the dark. HSCs with OptoTrkA activity show an increased ability for proliferation and migration and also exhibited accelerated neuronal and glial cell differentiation. These findings suggest that the precise control of TrkA activity using optogenetic tools is a viable strategy for the regeneration of neurons from HSCs, and also provides a novel insight into the clinical application of optogenetic tools in cell-transplantation therapy.

19.
Am J Hum Genet ; 107(4): 743-752, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946764

RESUMO

Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.

20.
Nat Plants ; 6(10): 1250-1261, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32895530

RESUMO

Information in the genome is not only encoded within sequence or epigenetic modifications, but is also found in how it folds in three-dimensional space. The formation of self-interacting genomic regions, named topologically associated domains (TADs), is known as a key feature of genome organization beyond the nucleosomal level. However, our understanding of the formation and function of TADs in plants is extremely limited. Here we show that the genome of Marchantia polymorpha, a member of a basal land plant lineage, exhibits TADs with epigenetic features similar to those of higher plants. By analysing various epigenetic marks across Marchantia TADs, we find that these regions generally represent interstitial heterochromatin and their borders are enriched with Marchantia transcription factor TCP1. We also identify a type of TAD that we name 'TCP1-rich TAD', in which genomic regions are highly accessible and are densely bound by TCP1 proteins. Transcription of TCP1 target genes differs on the basis gene location, and those in TCP1-rich TADs clearly show a lower expression level. In tcp1 mutant lines, neither TCP1-bound TAD borders nor TCP1-rich TADs display drastically altered chromatin organization patterns, suggesting that, in Marchantia, TCP1 is dispensable for TAD formation. However, we find that in tcp1 mutants, genes residing in TCP1-rich TADs have a greater extent of expression fold change as opposed to genes that do not belong to these TADs. Our results suggest that, besides standing as spatial chromatin-packing modules, plant TADs function as nuclear microcompartments associated with transcription factor activities.

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