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1.
Psychiatry Res ; 299: 113837, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33721783

RESUMO

ABO blood types and their corresponding antigens have long been assumed to be related to different human diseases. So far, smaller studies on the relationship between mental disorders and blood types yielded contradicting results. In this study we analyzed the association between ABO blood types and lifetime major depressive disorder (MDD). We performed a pooled analysis with data from 26 cohorts that are part of the MDD working group of the Psychiatric Genomics Consortium (PGC). The dataset included 37,208 individuals of largely European ancestry of which 41.6% were diagnosed with lifetime MDD. ABO blood types were identified using three single nucleotide polymorphisms in the ABO gene: rs505922, rs8176746 and rs8176747. Regression analyses were performed to assess associations between the individual ABO blood types and MDD diagnosis as well as putative interaction effects with sex. The models were adjusted for sex, cohort and the first ten genetic principal components. The percentage of blood type A was slightly lower in cases than controls while blood type O was more prominent in cases. However, these differences were not statistically significant. Our analyses found no evidence of an association between ABO blood types and major depressive disorder.

2.
Nat Commun ; 12(1): 757, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536423

RESUMO

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.


Assuntos
Cordoma/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteína SMARCB1/genética , Neoplasias da Base do Crânio/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Genoma/métodos , Adulto , Cordoma/patologia , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Neoplasias da Base do Crânio/patologia , Adulto Jovem
3.
Int J Cancer ; 148(11): 2712-2723, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460452

RESUMO

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

4.
Med Sci Monit ; 27: e927421, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33513128

RESUMO

BACKGROUND This study explored the mechanism of action of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) at the pharmacological level in the treatment of psoriasis. MATERIAL AND METHODS The active ingredients in MGCM were mined through literature retrieval and the BATMAN-TCM database, and potential targets were predicted. In addition, targets associated with psoriasis were acquired using multiple disease-related databases. Thereafter, an interaction network between candidate MGCM targets and the known psoriasis-associated targets was constructed based on the protein-protein interaction (PPI) data, using the STRING database. Then, the topological parameter degree was determined for mining the core targets for MGCM in the treatment of psoriasis, which also represented the major hubs within the PPI network. In addition, the core networks of targets and ingredients were constructed using Cytoscape software to apply MGCM in the treatment for psoriasis. These core targets were then analyzed for Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathway enrichment using OmicShare. RESULTS The ingredient-target core network of MGCM for treating psoriasis was constructed; it contained 52 active ingredients and corresponded to 19 core targets. In addition, based on enrichment analysis, these core targets were majorly enriched for several biological processes (immuno-inflammatory responses, leukocyte differentiation, energy metabolism, angiogenesis, and programmed cell death) together with the relevant pathways (Janus kinase-signal transducer and activator of transcription, toll-like receptors, nuclear factor kappaB, vascular endothelial growth factor, and peroxisome proliferator-activated receptor), thus identifying the possible mechanism of action of MGCM in treating psoriasis. CONCLUSIONS The present network pharmacology study indicated that MGCM alleviates various pathological factors of psoriasis through multiple compounds, multiple targets, and multiple pathways.

5.
BMC Pulm Med ; 21(1): 7, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407328

RESUMO

BACKGROUND: For patients with acute exacerbation of COPD (AECOPD), type 2 diabetes mellitus (T2DM) as comorbidity have poor outcomes. However, data on the impact of previously diagnosed and new- diagnosed T2DM in such a patient population is lacking. METHODS: Inpatients diagnosed with AECOPD in the department of Pulmonary and Critical Care Medicine of The First Hospital of China Medical University during 2011-2017 were enrolled. Data on demography, prevalence of type 2 DM, other comorbidities, hospital stays and laboratory tests (including arterial partial pressure of oxygen [PaO2]) results were recorded. Results were compared with AECOPD patients having previously diagnosed and new-diagnosed type 2 diabetes. Markers associated with development of type 2 DM and the prognosis of AECOPD patients were identified. RESULTS: Of the 196 patients enrolled in this study, the overall prevalence of T2DM was 26%. The PaO2 in the newly diagnosed T2DM group was considerably lower versus non-diabetic group. The T2DM group had a longer hospital stay and higher troponin level versus the non-diabetic group. AECOPD patients with T2DM were found to be correlated with hypertension. Age, need for assisted ventilation, increased troponin, and elevated fasting blood glucose on admission were risk factors for death in hospitalized AECOPD patients. CONCLUSIONS: AECOPD patients had a higher prevalence of T2DM than the general population; T2DM comorbidity caused lower PaO2, longer hospital stays, and increased troponin. Poor blood glucose control may increase the risk of death in AECOPD patients.

6.
Environ Int ; 147: 105975, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33385923

RESUMO

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10-26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10-3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

7.
Thorax ; 76(3): 256-263, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33318237

RESUMO

OBJECTIVE: To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers. DESIGN AND SETTING: A nested case-control study within two prospective cohort studies, the Shanghai Women's Health Study (n=74 941) and the Shanghai Men's Health Study (n=61 480). PARTICIPANTS: Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women). MAIN OUTCOMES AND MEASURES: Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity. RESULTS: Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: ptrend=0.05; Simpson: ptrend=0.04; Observed Species: ptrend=0.64). No case-control differences were apparent for beta diversity (pMiRKAT=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (ORlow 1.00 (reference), ORmedium 0.61 (95% CI 0.32 to 1.18), ORhigh 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (ORlow 1.00 (reference), ORmedium 0.66 (95% CI 0.35 to 1.25), ORhigh 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (ORlow 1.00 (reference), ORmedium 1.49 (95% CI 0.73 to 3.08), ORhigh 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (ORlow 1.00 (reference), ORmedium 2.15 (95% CI 1.03 to 4.47), ORhigh 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer. CONCLUSIONS: Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.

8.
Genes (Basel) ; 12(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374332

RESUMO

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33200499

RESUMO

Single crystal luminescence materials usually show higher luminous efficiency and better stability than a powdery one. Poor water resistance of Mn 4+ doped powdery fluoride red phosphors limits their further application for white light-emitting diodes (WLEDs) with high color rendering index. In this report, we have presented a solvent-vapor transport route for centimeter-sized single-crystal red phosphor development. As a side benefit, the epitaxial growth route to yield its core-shell structure at ambient temperature was adopted. These single-crystal red phosphors could be applied in all-inorganic WLED devices without any organic resin. Cs 2 TiF 6 :Mn 4+ (CTFM) single crystal provides a significant enhancement of quantum efficiency, moisture resistance, and thermal stability as compared to its polycrystalline powders. Particularly, the internal quantum efficiency can reach as high as 98.7%. To further improve waterproof stability, the Cs 2 TiF 6 (CTF) shell with tunable thickness has been epitaxially grown on the CTFM single crystal surface and a unique three-step photoluminescence intensity evolution mechanism has been proposed. By combining as-prepared CTFM@CTF core-shell structured single crystal, YAG:Ce single crystal and blue-chip, warm WLEDs with excellent color rendition (R a = 90, R 9 = 94), low correlated color temperature (CCT = 3155 K), and high luminous efficacy have been fabricated without any organic resins. Furthermore, CTFM@CTF and YAG:Ce single crystals based high-power laser-driven white-lighting devices (LDs) with high brightness and excellent directionality have also been successfully obtained.

10.
Exp Ther Med ; 20(6): 133, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33082865

RESUMO

The present study aimed to compare the safety of brivaracetam (BRV) at various doses among patients with epilepsy through a network meta-analysis. Randomized controlled trials (RCTs) were retrieved from different databases, which were then pooled for a network analysis for calculating the odds ratios (ORs), together with the corresponding 95% confidence intervals (CIs) and surface under the cumulative ranking curve (SUCRA). A total of 9 RCTs were included in the final analysis. Compared with placebo, BRV at a dose of 50 mg daily led to a markedly increased risk of nervous system disorders (OR, 0.62; 95% CI, 0.43-0.90; P=0.01) and evidently increased the risk of psychiatric disorders (OR, 0.16; 95% CI, 0.04-0.64; P=0.022). However, BRV treatment was not associated with a statistically significant change in the prevalence of infectious diseases. SUCRA analysis suggested that treatment with BRV at 50 mg/day posed the highest risk of nervous system disorders and psychiatric disorders compared with placebo or other doses of BRV. In conclusion, BRV treatment at a dose of 50 mg/day may increase the risk of nervous system diseases and psychosis disorders compared with the placebo group. However, more high-quality clinical studies are warranted to validate these results.

11.
Am J Epidemiol ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32976571

RESUMO

A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2df-test) or additionally on squares and cross-product of mean distances (5df-test). We compared the power of 2df- and 5df-tests to the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2df-test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2df-test had slightly greater power than MiRKAT for Dirichlet-Multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5df-test yielded smaller p-values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have comparable power to MiRKAT (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.

12.
Science ; 369(6503): 561-565, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32732423

RESUMO

Most neuropsychiatric disease risk variants are in noncoding sequences and lack functional interpretation. Because regulatory sequences often reside in open chromatin, we reasoned that neuropsychiatric disease risk variants may affect chromatin accessibility during neurodevelopment. Using human induced pluripotent stem cell (iPSC)-derived neurons that model developing brains, we identified thousands of genetic variants exhibiting allele-specific open chromatin (ASoC). These neuronal ASoCs were partially driven by altered transcription factor binding, overrepresented in brain gene enhancers and expression quantitative trait loci, and frequently associated with distal genes through chromatin contacts. ASoCs were enriched for genetic variants associated with brain disorders, enabling identification of functional schizophrenia risk variants and their cis-target genes. This study highlights ASoC as a functional mechanism of noncoding neuropsychiatric risk variants, providing a powerful framework for identifying disease causal variants and genes.


Assuntos
Alelos , Encéfalo/metabolismo , Cromatina/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Esquizofrenia/genética , Elementos Facilitadores Genéticos , Humanos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Risco
13.
mSystems ; 5(4)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636335

RESUMO

Epidemiologic studies use various biosample collection methods to study associations between human oral microbiota and health outcomes. However, the agreement between the different methods is unclear. We compared a commercially available OMNIgene ORAL kit to three alternative collection methods: Saccomanno's fixative, Scope mouthwash, and nonethanol mouthwash. Oral samples were collected from 40 individuals over 4 visits. Two samples were collected from each subject per visit: one with OMNIgene and one with an alternative method. DNA was extracted using the DSP DNA Virus Pathogen kit, and the V4 region of the 16S rRNA gene was PCR amplified and sequenced using MiSeq. Oral collection methods were compared based on alpha and beta diversity metrics and phylum- and genus-level relative abundances. All alpha diversity metrics were significantly lower for Saccomanno's fixative than for OMNIgene (P < 0.001), whereas the two mouthwashes were more similar to OMNIgene. Principal-coordinate analysis (PCoA) using the Bray-Curtis and weighted UniFrac beta diversity matrices showed large differences in the microbial compositions of samples collected with Saccomanno's compared to those with OMNIgene and the mouthwashes. Clustering by collection method was not observed in unweighted UniFrac PCoA plots, suggesting differences in relative abundances but not specific taxa detected by the collection methods. Relative abundances of most taxa were significantly different between OMNIgene and the other methods at each taxonomic level, with Saccomanno's showing the least agreement with OMNIgene. There were clear differences in oral microbial communities between the four oral collection methods, particularly for Saccomanno's fixative.IMPORTANCE We compared four different oral collection methods for studying the human oral microbiome: an OMNIgene ORAL kit, Scope mouthwash, nonethanol mouthwash, and Saccomanno's fixative. Our study shows that the type of the collection method can have a large impact on the results of an oral microbiome analysis. We recommend that one consistent oral collection method should be used for all oral microbiome comparisons. While Scope and nonethanol mouthwashes are less expensive and provide results similar to those with OMNIgene, Saccomanno's fixative may be unfavorable due to the microbial differences detected in this study. Our results will help guide the design of future oral microbiome studies.

14.
J Genet Genomics ; 47(5): 273-280, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32684419

RESUMO

Although Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has been widely used for basic research in model plants, its application for applied breeding in crops has faced strong regulatory obstacles, due mainly to a poor understanding of the authentic output of this system, particularly in higher generations. In this study, different from any previous studies, we investigated in detail the molecular characteristics and production performance of CRISPR/Cas9-generated SD1 (semi-dwarf 1) mutants from T2 to T4 generations, of which the selection of T1 and T2 was done only by visual phenotyping for semidwarf plants. Our data revealed not only on- and off-target mutations with small or lager indels but also exogenous elements in T2 plants. All indel mutants passed stably to T3 or T4 without additional modifications independent on the presence of Cas9, while some lines displayed unexpected hereditary patterns of Cas9 or some exogenous elements. In addition, effects of various SD1 alleles on rice height and yield differed depending on genetic backgrounds. Taken together, our data showed that the CRISPR/Cas9 system is effective in producing homozygous mutants for functional analysis, but it may be not as precise as expected in rice, and that early and accurate molecular characterization and screening must be carried out for generations before transitioning of the CRISPR/Cas9 system from laboratory to field.

15.
Plant Mol Biol ; 104(1-2): 187-201, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32681357

RESUMO

KEY MESSAGE: The mutation of FAX1 (Fatty Acid Export 1) disrupts ROS homeostasis and suppresses transcription activity of DYT1-TDF1-AMS-MS188 genetic network, leading to atypical tapetum PCD and defective pollen formation in Arabidopsis. Fatty acids (FAs) have multiple important biological functions and exert diverse cellular effects through modulating Reactive Oxygen Species (ROS) homeostasis. Arabidopsis FAX1 (Fatty Acid Export 1) mediates the export of de novo synthesized FA from chloroplast and loss of function of FAX1 impairs male fertility. However, mechanisms underlying the association of FAX1-mediated FA export with male sterility remain enigmatic. In this study, by using an integrated approach that included morphological, cytological, histological, and molecular analyses, we revealed that loss of function of FAX1 breaks cellular FA/lipid homeostasis, which disrupts ROS homeostasis and suppresses transcriptional activation of the DYT1-TDF1-AMS-MS188 genetic network of anther development, impairing tapetum development and pollen wall formation, and resulting in male sterility. This study provides new insights into the regulatory network for male reproduction in plants, highlighting an important role of FA export-mediated ROS homeostasis in the process.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Membrana/metabolismo , Pólen/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Flores/citologia , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Redes Reguladoras de Genes , Proteínas de Membrana/genética , Mutação , Fenótipo , Pólen/genética , Reprodução , Fatores de Transcrição
16.
Methods Mol Biol ; 2204: 217-224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32710328

RESUMO

In recent years, medical advances make lung transplantation become a standard treatment for terminal lung diseases (such as emphysema, pulmonary fibrosis, pulmonary cystic fibrosis, and pulmonary arterial hypertension) that cannot be cured by drugs or surgery (Lund et al., J Heart Lung Transplant 34:1244, 2015). However, the current number of donor lungs that meet the transplant criteria is no longer sufficient for transplanting, causing some patients to die while waiting for a suitable lung. Current methods for improving the situation of shortage of lung transplant donors include the use of donation after cardiac death (DCD) donors, smoker donors, and Ex Vivo Lung Perfusion (EVLP). Among them, EVLP is a technique for extending lung preservation time and repairing lung injury in the field of lung transplantation. By continuously assessing and improving the function of marginal donor lungs, EVLP increases the number of lungs that meet the transplant criteria and, to some extent, alleviates the current situation of shortage of donor lungs. This chapter reviews the clinical application and research progress of EVLP in the field of lung transplantation.

17.
Plant Physiol ; 184(1): 223-235, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32690757

RESUMO

Stigma exsertion is an important agricultural trait that facilitates the application of heterosis in crop breeding. Although several quantitative trait loci associated with stigma exsertion have been fine-mapped or cloned, the underlying genetic basis, particularly in legumes, remains unclear. In this study, we identified and characterized the exserted stigma mutant stigma exsertion1 (sge1) in the model legume Medicago truncatula The exserted stigma phenotype of sge1 is mainly caused by physical interaction between floral organs, in which normal petal and stamen elongation are inhibited due to flower cuticle defects. SGE1 encodes an ATP-binding cassette G (ABCG) transporter that plays a critical role in regulating floral cutin and wax secretion in M. truncatula SGE1 physically interacts with another half-size transporter, MtABCG13, to form a functional heterodimer. Mutation of MtABCG13 results in flower cuticle defects similar to those in sge1 as well as stigma exsertion, indicating that SGE1 and MtABCG13 are indispensable for flower cuticle secretion and collaboratively control stigma exsertion in M. truncatula Our findings reveal novel functions for ABCG transporters in determining stigma exsertion by affecting the physical interactions of floral organs, providing insight into the molecular mechanism underlying stigma exsertion in leguminous plants with complex zygomorphic flowers.

18.
Semin Thorac Cardiovasc Surg ; 32(4): 1121-1122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569646
19.
Nat Commun ; 11(1): 3096, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32555180

RESUMO

Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance.


Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Variações do Número de Cópias de DNA/genética , Epigenômica , Mutação em Linhagem Germinativa/genética , Humanos , Filogenia
20.
Theor Appl Genet ; 133(8): 2323-2334, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32405769

RESUMO

KEY MESSAGE: A multiplex ligation-dependent probe amplification (MLPA)-based method was developed and successfully utilized to efficiently detect both CRISPR/Cas9-induced and naturally occurred mutations in rice. The site-specific nuclease-based CRISPR/Cas9 system has emerged as one of the most efficient genome editing tools to modify multiple genomic targets simultaneously in various organisms, including plants for both fundamental and applied researches. Screening for both on-target and off-target mutations in CRISPR/Cas9-generated mutants at the early stages is an indispensable step for functional analysis and subsequent application. Various methods have been developed to detect CRISPR/Cas9-induced mutations in plants. Still, very few have focused on the detection of both on- and off-targets simultaneously, let alone the detection of natural mutations. Here, we report a multiplex capable method that allows to detect CRISPR/Cas9 induced on- and off-target mutations as well as naturally occurred mutation based on a multiplex ligation-dependent probe amplification (MLPA) method. We demonstrated that unlike other methods, the modified target-specific MLPA method can accurately identify any INDELs generated naturally or by the CRISPR/Cas9 system and that it can detect natural variation and zygosity of the CRISPR/Cas9-generated mutants in rice as well. Furthermore, its high sensitivity allowed to define INDELs down to 1 bp and substitutions to a single nucleotide. Therefore, this sensitive, reliable, and cheap method would further accelerate functional analysis and marker-assisted breeding in plants, including rice.

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