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1.
Org Lett ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955758

RESUMO

A new asymmetric catalytic conjugate reduction of yne-allenones to synthesize enantioenriched cyclobuta[a]naphthalen-4(2H)-ones has been established that uses copper-bisphosphine complexes as catalysts and gives excellent regio- and enantioselectivities (≥99% ee) in most cases. This protocol tolerates a broad scope of substrates, exhibits high compatibility with various substituents, and gives excellent stereoselectivity, providing a catalytic and efficient entry to fabrication of synthetically important chiral 6-6-4 tricarbocyclic scaffolds.

2.
Chem Commun (Camb) ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942828

RESUMO

New tunable catalytic [2+2] cycloaddition/silane-mediated conjugate transfer reductions of yne-allenones have been developed, by which substituent-diverse cyclobutarenes with generally good yields were selectively synthesized by adjusting Fe-H and Cu-H catalytic systems. Use of the Fe-H system triggers 1,6-conjugate reduction to dihydrocyclobuta[a]naphthalen-4-ols whereas the Cu-H complex enables 1,4-conjugate reduction to cyclobuta[a]naphthalen-4(2H)-ones.

3.
Nucleic Acids Res ; 49(7): 4104-4119, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33784398

RESUMO

Eukaryotic rRNAs and snRNAs are decorated with abundant 2'-O-methylated nucleotides (Nm) that are predominantly synthesized by box C/D snoRNA-guided enzymes. In the model plant Arabidopsis thaliana, C/D snoRNAs have been well categorized, but there is a lack of systematic mapping of Nm. Here, we applied RiboMeth-seq to profile Nm in cytoplasmic, chloroplast and mitochondrial rRNAs and snRNAs. We identified 111 Nm in cytoplasmic rRNAs and 19 Nm in snRNAs and assigned guide for majority of the detected sites using an updated snoRNA list. At least four sites are directed by guides with multiple specificities as shown in yeast. We found that C/D snoRNAs frequently form extra pairs with nearby sequences of methylation sites, potentially facilitating the substrate binding. Chloroplast and mitochondrial rRNAs contain five almost identical methylation sites, including two novel sites mediating ribosomal subunit joining. Deletion of FIB1 or FIB2 gene reduced the accumulation of C/D snoRNA and rRNA methylation with FIB1 playing a bigger role in methylation. Our data reveal the comprehensive 2'-O-methylation maps for Arabidopsis rRNAs and snRNAs and would facilitate study of their function and biosynthesis.

4.
Sci Rep ; 11(1): 5596, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692422

RESUMO

Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.

5.
J Mol Histol ; 52(2): 373-383, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33543337

RESUMO

Exercise preconditioning (EP) can alleviate myocardial ischemic/hypoxic injury by inducing endogenous cardioprotection. Hematoxylin-eosin (HE), hematoxylin-basic fuchsin-picric acid (HBFP), and chromotrope-2R brilliant green (C-2R BG) staining have been used to visualize myocardial ischemic/hypoxic changes in previous EP studies, but comprehensive evaluation and comparisons of these methods are lacking. This study evaluated ischemic/hypoxic changes in adjacent myocardial sections by HE, HBFP, and C-2R BG and compared the characteristics of sections stained by these three methods to show changes associated with exercise-induced myocardial ischemic/hypoxic injury. Rats were randomly divided into four groups: control (C), exercise preconditioning (EP), exhaustive exercise (EE), and exercise preconditioning + exhaustive exercise (EP + EE). Adjacent myocardial sections were stained as described above and compared to evaluate the effects of exercise-induced myocardial ischemic/hypoxic injury. The three staining methods revealed consistent localization patterns of myocardial ischemic/hypoxic injury in all groups. Results suggest that EP can alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury, and the three staining methods are suitable for the histological study of exercise-induced myocardial ischemic/hypoxic injury and protection. HE staining is a simple procedure but is not specific for myocardial ischemic/hypoxic injury. HBFP and C-2R BG staining can be used to specifically visualize myocardial ischemic/hypoxic injury.

6.
Nat Mater ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558718

RESUMO

Moiré superlattices in transition metal dichalcogenide (TMD) heterostructures can host novel correlated quantum phenomena due to the interplay of narrow moiré flat bands and strong, long-range Coulomb interactions1-9. However, microscopic knowledge of the atomically reconstructed moiré superlattice and resulting flat bands is still lacking, which is critical for fundamental understanding and control of the correlated moiré phenomena. Here we quantitatively study the moiré flat bands in three-dimensional (3D) reconstructed WSe2/WS2 moiré superlattices by comparing scanning tunnelling spectroscopy (STS) of high-quality exfoliated TMD heterostructure devices with ab initio simulations of TMD moiré superlattices. A strong 3D buckling reconstruction accompanied by large in-plane strain redistribution is identified in our WSe2/WS2 moiré heterostructures. STS imaging demonstrates that this results in a remarkably narrow and highly localized K-point moiré flat band at the valence band edge of the heterostructure. A series of moiré flat bands are observed at different energies that exhibit varying degrees of localization. Our observations contradict previous simplified theoretical models but agree quantitatively with ab initio simulations that fully capture the 3D structural reconstruction. Our results reveal that the strain redistribution and 3D buckling in TMD heterostructures dominate the effective moiré potential and the corresponding moiré flat bands at the Brillouin zone K points.

7.
Front Psychiatry ; 11: 580570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192722

RESUMO

Background: Schizophrenia, regarded as a neurodevelopmental disorder, is characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Investigating the spontaneous brain activity in patients with schizophrenia can help us understand the underlying pathophysiologic mechanism of schizophrenia. However, results concerning abnormal neural activities and their correlations with cognitive dysfunction/psychopathology of patients with schizophrenia were inconsistent. Methods: We recruited 57 first-diagnosed and drug-naive patients with schizophrenia and 50 matched healthy controls underwent magnetic resonance imaging. The Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery were used to assess the psychopathology/cognitive dysfunction. Regional homogeneity (ReHo) was used to explore neural activities. Correlation analyses were calculated between abnormal ReHo values and PANSS scores/standardized cognitive scores. Lastly, support vector machine analyses were conducted to evaluate the accuracy of abnormal ReHo values in distinguishing patients with schizophrenia from healthy controls. Results: Patients with schizophrenia showed cognitive dysfunction, and increased ReHo values in the right gyrus rectus, right inferior frontal gyrus/insula and left inferior frontal gyrus/insula compared with those of healthy controls. The ReHo values in the right inferior frontal gyrus/insula were positively correlated with negative symptom scores and negatively correlated with Hopkins verbal learning test-revised/verbal learning. Our results showed that the combination of increased ReHo values in the left inferior frontal gyrus/insula and right gyrus rectus had 78.5% (84/107) accuracy, 85.96% (49/57) sensitivity, and 70.00% specificity, which were higher than other combinations. Conclusions: Hyperactivities were primarily located in the prefrontal regions, and increased ReHo values in the right inferior frontal gyrus/insula might reflect the severity of negative symptoms and verbal learning abilities. The combined increases of ReHo values in these regions might be an underlying biomarker in differentiating patients with schizophrenia from healthy controls.

8.
BMC Genomics ; 21(Suppl 10): 753, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208104

RESUMO

BACKGROUND: The emergence of the third generation sequencing technology, featuring longer read lengths, has demonstrated great advancement compared to the next generation sequencing technology and greatly promoted the biological research. However, the third generation sequencing data has a high level of the sequencing error rates, which inevitably affects the downstream analysis. Although the issue of sequencing error has been improving these years, large amounts of data were produced at high sequencing errors, and huge waste will be caused if they are discarded. Thus, the error correction for the third generation sequencing data is especially important. The existing error correction methods have poor performances at heterozygous sites, which are ubiquitous in diploid and polyploidy organisms. Therefore, it is a lack of error correction algorithms for the heterozygous loci, especially at low coverages. RESULTS: In this article, we propose a error correction method, named QIHC. QIHC is a hybrid correction method, which needs both the next generation and third generation sequencing data. QIHC greatly enhances the sensitivity of identifying the heterozygous sites from sequencing errors, which leads to a high accuracy on error correction. To achieve this, QIHC established a set of probabilistic models based on Bayesian classifier, to estimate the heterozygosity of a site and makes a judgment by calculating the posterior probabilities. The proposed method is consisted of three modules, which respectively generates a pseudo reference sequence, obtains the read alignments, estimates the heterozygosity the sites and corrects the read harboring them. The last module is the core module of QIHC, which is designed to fit for the calculations of multiple cases at a heterozygous site. The other two modules enable the reads mapping to the pseudo reference sequence which somehow overcomes the inefficiency of multiple mappings that adopt by the existing error correction methods. CONCLUSIONS: To verify the performance of our method, we selected Canu and Jabba to compare with QIHC in several aspects. As a hybrid correction method, we first conducted a groups of experiments under different coverages of the next-generation sequencing data. QIHC is far ahead of Jabba on accuracy. Meanwhile, we varied the coverages of the third generation sequencing data and compared performances again among Canu, Jabba and QIHC. QIHC outperforms the other two methods on accuracy of both correcting the sequencing errors and identifying the heterozygous sites, especially at low coverage. We carried out a comparison analysis between Canu and QIHC on the different error rates of the third generation sequencing data. QIHC still performs better. Therefore, QIHC is superior to the existing error correction methods when heterozygous sites exist.

9.
Mol Genet Genomic Med ; 8(10): e1395, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32757330

RESUMO

BACKGROUND: ß3-αC loop is a highly conserved structural domain across oncogene families, which is a switch for kinase activity. There have been numerous researches on mutations within ß3-αC loop in EGFR, but relatively less in ERBB2, BRAF, and MAP2K1. In addition, previous studies mainly focus on ß3-αC deletion in EGFR, which is the most common type affecting kinase activity and driving lung cancer. Other mutation types are not well studied. METHODS: Here we analyzed the profile of ß3-αC loop mutations in a total of 10,000 tumor biopsy and/or ctDNA patient samples using hybridization capture-based next-generation sequencing. RESULTS: We identified 1616 mutations within ß3-αC loop in this cohort. Most mutations were located in EGFR, with less percentage in ERBB2, BRAF, and MAP2K1. EGFR ß3-αC deletions occurred at a high percentage of 96.7% and were all drug-relevant. We also detected rare EGFR ß3-αC insertions and point mutations, most of which were related to EGFR TKIs resistance. ERBB2 ß3-αC deletions were only found in breast cancers and sensitive to EGFR/ERBB2 inhibitor. Moreover, BRAF and MAP2K1 mutations within ß3-αC loop also demonstrated drugs relevance. CONCLUSION: Our study showed that oncogenic mutations within the ß3-αC loop of ERBB2, MAP2K1, and BRAF are analogous to that of EGFR, which have profound effect on drug response. Understanding the mutation profile within the ß3-αC loop is critical for targeted therapies.

10.
BMC Med Genomics ; 13(Suppl 6): 79, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854699

RESUMO

BACKGROUND: Genotyping of structural variation is an important computational problem in next generation sequence data analysis. However, in cancer genomes, the copy number variant(CNV) often coexists with other types of structural variations which significantly reduces the accuracy of the existing genotype methods. The bias on sequencing coverage and variant allelic frequency can be observed on a CNV region, which leads to the genotyping approaches that misinterpret the heterozygote as a homozygote. Furthermore, other data signals such as split mapped read, abnormal read will also be misjudged because of the CNV. Therefore, genotyping the structural variations with CNV is a complicated computational problem which should consider multiple features and their interactions. METHODS: Here we proposed a computational method for genotyping indels in the CNV region, which introduced a machine learning framework to comprehensively incorporate a set of data features and their interactions. We extracted fifteen kinds of classification features as input and different from the traditional genotyping problem, here the structure of variant may fall into types of normal homozygote, homozygous variant, heterozygous variant without CNV, heterozygous variant with a CNV on the mutated haplotype, and heterozygous variant with a CNV on the wild haplotype. The Multiclass Relevance Vector Machine (M-RVM) was used as a machine learning framework combined with the distribution characteristics of the features. RESULTS: We applied the proposed method to both simulated and real data, and compared it with the existing popular softwares include Gindel, Facets, GATK, and also compared with other machine learning cores: Support Vector Machine, Lanrange-SVM with OVO multiple classification, Naïve Bayes and BP Neural Network. The results demonstrated that the proposed method outperforms others on accuracy, stability and efficiency. CONCLUSION: This work shows that the genotyping of structural variations on the CNV region cannot be solved as a traditional genotyping problem. More features should be used to efficiently complete the five-category task. According to the result, the proposed method can be a practical algorithm to correct genotype structural variations with CNV on the next generation sequence data. The source codes have been uploaded at https://github.com/TrinaZ/Mixgenotype for academic usage only.

11.
BMC Bioinformatics ; 21(1): 295, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640979

RESUMO

BACKGROUND: The human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing, the golden standard technology for HLA typing enables accurate identification of HLA alleles in high-resolution. However, only the commercial software, such as uTYPE, SBT-Assign, and SBTEngine, and very few open-source tools could be applied to perform HLA typing based on Sanger sequencing. RESULTS: We developed a user-friendly, cross-platform and open-source desktop application, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles. SOAPTyping can produce accurate results with a comprehensible protocol and featured functions. Moreover, SOAPTyping supports a more advanced group-specific sequencing primers (GSSP) module to solve the ambiguous typing results. We used SOAPTyping to analyze 36 samples with known HLA typing from the University of California Los Angeles (UCLA) International HLA DNA Exchange platform and 100 anonymous clinical samples, and the HLA typing results from SOAPTyping are identical to the golden results and 5.5 times faster than commercial software uTYPE, which shows the usability of SOAPTyping. CONCLUSIONS: We introduce the SOAPTyping as the first open-source and cross-platform HLA typing software with the capability of producing high-resolution HLA typing predictions from Sanger sequence data.


Assuntos
Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA , Software , Alelos , Primers do DNA , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Humanos
12.
BMC Med Inform Decis Mak ; 20(Suppl 3): 137, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646420

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are those RNA molecules that lack the poly (A) tails, which present the closed-loop structure. Recent studies emphasized that some circRNAs imply different functions from canonical transcripts, and further associated with complex diseases. Several computational methods have been developed for detecting circRNAs from RNA-seq data. However, the existing methods prefer to high sensitivity strategies, which always introduce many false positives. Thus, in clinical decision-supporting system, a comprehensive filtering approach is needed for accurately recognizing real circRNAs for decision models. METHODS: In this paper, we first reviewed the detection strategies of the existing methods. According to the features from RNA-seq data, we showed that any single feature (data signal) selected by the existing strategies cannot accurately distinguish a circRNA. However, we found that some combinations of those features (data signals) could be used as signatures for recognizing circRNAs. To avoid the high computational complexity of the combinational optimization problem, we present CIRCPlus2, which adopts a machine learning framework to recognize real circRNAs according to multiple data signals captured from RNA-seq data. By comparing multiple machine learning frameworks, CIRCPlus2 adopts a Gradient Boosting Decision Tree (GBDT) framework. RESULTS: Given a set of candidate circRNAs, reported by any existing detection tool(s), the features of each candidate are extracted from the aligned reads. The GBDT framework can be trained by a training dataset. By applying the selected features on the framework, the predictions on true/false positives are reported. To verify the performance of the proposed approach, we conducted several groups of experiments on both real RNA-seq datasets and a series of simulation datasets with different preset configurations. The results demonstrated that CIRCPlus2 clearly improved the specificities, while it also maintained high levels of sensitivities. CONCLUSIONS: Filtering false positives is quite important in RNA-seq data analysis pipeline. Machine learning framework is suitable for solving this filtering problem. CIRCPlus2 is an efficient approach to identify the false positive circRNAs from the real ones.

13.
BMC Med Inform Decis Mak ; 20(Suppl 3): 136, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646427

RESUMO

BACKGROUND: Bladder cancer (BC) is regarded as one of the most fatal cancer around the world. Nevertheless, there still lack of sufficient markers to predict the prognosis of BC patients. Herein, we aim to establish a prognosis predicting signature based on long-noncoding RNA (lncRNA) for the invasive BC patients. METHODS: The lncRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, along with the correlated clinicopathological information. The univariate Cox regression test was employed to screen out the recurrence-free survival (RFS)-related lncRNAs. Then, the LASSO method was conducted to construct the signature based on these RFS-related lncRNA candidates. Genes correlated with these fourteen lncRNAs were extracted from the mRNA expression profile, with the Pearson correlation coefficient > 0.60 or < - 0.40. Subsequently, the Proteomap pathway enrichment analyses were conducted to classify the function of these correlated genes. Furthermore, the multivariate analyses were executed to reveal the independent role of the proposed signature with the clinicopathological features. RESULTS: We established an lncRNA-based RFS predicting signature by the LASSO Cox regression test, and proved its usage and stability on both the training and validation cohorts by the Kaplan-Meier and receiver operating characteristic (ROC) curves. Notably, the multivariate Cox regression analysis found that our classifier was an independent indicator for muscle-invasive BC patients rather than sex, age and tumor grade, with higher predictive value than the existing ones. Besides, we did the pathway analyses for these genes that highly correlated with the proposed fourteen lncRNAs, as well as the differentially expressed genes (DEGs) derived from the high-risk vs. low-risk groups, and the recurrence vs. non-recurrence groups, respectively. Notably, these results were consistent, and these genes were mostly enriched in the transcription factors, G protein-coupled receptors, MAPK signaling pathways, which were proved significantly associated with tumor progression and drug resistance. CONCLUSIONS: Our results suggested that the fourteen-lncRNA-based RFS predicting signature is an independent indicator for BC patients. Further prospective studies with more samples are needed to verify our findings.

14.
Comput Biol Chem ; 87: 107281, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32623023

RESUMO

Predicting the binding of T cell receptors (TCRs) to epitopes plays a vital role in the immunotherapy, because it guides the development of therapeutic vaccines and cancer treatments. Many prediction methods attempted to explain the relationship between TCR repertoires from different aspects such as the V(D)J gene locus and the biophysical features of amino acids molecules, but the extraction of these features is time consuming and the performance of these models are limited. Few studies have investigated how k-mers formed by adjacent amino acids in TCR sequences direct the epitope recognition, and the specific mechanism of TCR epitope binding is still unclear. Motivated by these, we presented SETE (Sequence-based Ensemble learning approach for TCR Epitope binding prediction), a novel model to predict the TCR epitope binding accurately. The model deconstructed the CDR3ß sequence to short amino acid chains as features and learned the pattern of them between different TCR repertoires with gradient boosting decision tree algorithm. Experiments have demonstrated that SETE can be helpful in predicting the TCRs' corresponding epitopes and it outperforms other state-of-the-art methods in predicting the epitope specificity of TCR on VDJdb data set. The source codes have been uploaded at https://github.com/wonanut/SETE for academic usage only.

15.
J Org Chem ; 85(11): 7036-7044, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32383594

RESUMO

A new single Pd-catalyzed decarboxylative allylation-nucleophilic cyclization relay is reported by using α-alkynyl arylols and vinylethylene carbonates (or vinyl carbamates), and a wide range of 3-allyl benzofurans with generally good yields were stereoselectively synthesized under mild conditions, among which the complete stereoselectivity of some cases was also observed. Notably, the present catalysts can tolerate air conditions without any ligand, additive, or base, opening new avenues to build up oxa-heterocycle frameworks through catalytic difunctionalization of internal alkynes.

16.
Cell Death Dis ; 11(5): 346, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393783

RESUMO

Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I-III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991-61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916-21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.

17.
Nucleic Acids Res ; 48(9): 5094-5105, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32297938

RESUMO

Box C/D RNA protein complexes (RNPs) catalyze site-specific 2'-O-methylation of RNA with specificity determined by guide RNAs. In eukaryotic C/D RNP, the paralogous Nop58 and Nop56 proteins specifically associate with terminal C/D and internal C'/D' motifs of guide RNAs, respectively. We have reconstituted active C/D RNPs with recombinant proteins of the thermophilic yeast Chaetomium thermophilum. Nop58 and Nop56 could not distinguish between the two C/D motifs in the reconstituted enzyme, suggesting that the assembly specificity is imposed by trans-acting factors in vivo. The two C/D motifs are functionally independent and halfmer C/D RNAs can also guide site-specific methylation. Extensive pairing between C/D RNA and substrate is inhibitory to modification for both yeast and archaeal C/D RNPs. N6-methylated adenine at box D/D' interferes with the function of the coupled guide. Our data show that all C/D RNPs share the same functional organization and mechanism of action and provide insight into the assembly specificity of eukaryotic C/D RNPs.


Assuntos
Metiltransferases/química , Metiltransferases/metabolismo , RNA Nucleolar Pequeno/química , RNA Nucleolar Pequeno/metabolismo , Ribonucleoproteínas/metabolismo , Adenina/análogos & derivados , Chaetomium/genética , Humanos , Metilação , Conformação de Ácido Nucleico , RNA/metabolismo , Ribonucleoproteínas/química , Sulfolobus solfataricus
18.
Clin Lab ; 66(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32255290

RESUMO

BACKGROUND: The current study aims to investigate the expression of lncRNA BLACAT1 in patients with acute myeloid leukemia (AML) and to analyze its correlation with clinical prognosis. METHODS: Peripheral blood samples were collected from 68 AML patients, including 48 patients with acute myeloid leukemia (AML), 20 patients with complete response (CR), and 30 patients with iron deficiency anemia (control group). LncRNA BLACAT1 was detected by real-time fluorescence quantitative PCR (qRT-PCR). The expression of BLACAT1 and its relationship with clinicopathological characteristics and prognosis were analyzed. RESULTS: The expression of lncRNA BLACAT1 in AML patients was significantly higher than that in complete remission patients and iron deficiency anemia patients, but the expression of lncRNA BLACAT1 in AML-CR group and control group had no significant difference. Further study showed that the expression of lncRNA BLACAT1 was correlated with the National Comprehensive Cancer Network (NCCN) risk classification, the amount of platelet and bone marrow primordial cells (%), and survival status of patients. The median overall survival time of patients with high expression of lncRNA BLACAT1 was significantly shorter than those with low expression of lncRNA BLACAT1 (p < 0.05). CONCLUSIONS: LncRNA BLACAT1 was involved in regulating the occurrence and development of AML and can be used as a potential prognostic marker and therapeutic target for AML patients.

19.
World Neurosurg ; 138: e317-e322, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32112936

RESUMO

OBJECTIVE: The relationship between neutrophil-lymphocyte ratio (NLR) and the occurrence of rebleeding in aneurysmal subarachnoid hemorrhage (aSAH) is poorly understood. Our study aimed to investigate the association between NLR on admission and rebleeding following aSAH. METHODS: Clinical and laboratorial data from patients with aSAH were retrospectively collected, including leukocyte, neutrophil, lymphocyte, and NLR. Univariate and multivariate analyses were performed to assess for the association of NLR with rebleeding. We performed propensity-score matching analyses to correct imbalances in patient characteristics between the rebleeding group and nonrebleeding group. RESULTS: Rebleeding occurred in 30 of 716 (4.19%) patients with aSAH in this cohort. Patients with rebleeding had significantly higher NLR comparing with patients without rebleeding (11.27 vs. 5.5; P < 0.05) in the univariate analysis. In the multivariate analysis, NLR was considered as a risk factor of rebleeding (odds ratio, 0.283; 95% confidence interval, 0.130-0.620; P = 0.002), as well as Fisher grade (odds ratio, 0.353, 95% confidence interval, 0.151-0.824; P = 0.016). The area under the curve of the NLR and combined NLR-Fisher grade model was 0.702 and 0.744 (sensitivity was 39.94%, and specificity was 100%) for predicting rebleeding, respectively. After propensity-score matching, the optimal cutoff value for NLR as a predictor for rebleeding following aSAH was determined as 5.4 (sensitivity was 83.33%, and the specificity was 63.33%). CONCLUSIONS: Higher NLR predicts the occurrence of rebleeding and poor outcome, and NLR combined with Fisher grade significantly improves the prediction of rebleeding following aSAH.


Assuntos
Biomarcadores/sangue , Linfócitos , Neutrófilos , Hemorragia Subaracnóidea/sangue , Idoso , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/cirurgia , Instrumentos Cirúrgicos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
20.
BMC Bioinformatics ; 21(Suppl 2): 82, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32164528

RESUMO

BACKGROUND: Genomic micro-satellites are the genomic regions that consist of short and repetitive DNA motifs. Estimating the length distribution and state of a micro-satellite region is an important computational step in cancer sequencing data pipelines, which is suggested to facilitate the downstream analysis and clinical decision supporting. Although several state-of-the-art approaches have been proposed to identify micro-satellite instability (MSI) events, they are limited in dealing with regions longer than one read length. Moreover, based on our best knowledge, all of these approaches imply a hypothesis that the tumor purity of the sequenced samples is sufficiently high, which is inconsistent with the reality, leading the inferred length distribution to dilute the data signal and introducing the false positive errors. RESULTS: In this article, we proposed a computational approach, named ELMSI, which detected MSI events based on the next generation sequencing technology. ELMSI can estimate the specific length distributions and states of micro-satellite regions from a mixed tumor sample paired with a control one. It first estimated the purity of the tumor sample based on the read counts of the filtered SNVs loci. Then, the algorithm identified the length distributions and the states of short micro-satellites by adding the Maximum Likelihood Estimation (MLE) step to the existing algorithm. After that, ELMSI continued to infer the length distributions of long micro-satellites by incorporating a simplified Expectation Maximization (EM) algorithm with central limit theorem, and then used statistical tests to output the states of these micro-satellites. Based on our experimental results, ELMSI was able to handle micro-satellites with lengths ranging from shorter than one read length to 10kbps. CONCLUSIONS: To verify the reliability of our algorithm, we first compared the ability of classifying the shorter micro-satellites from the mixed samples with the existing algorithm MSIsensor. Meanwhile, we varied the number of micro-satellite regions, the read length and the sequencing coverage to separately test the performance of ELMSI on estimating the longer ones from the mixed samples. ELMSI performed well on mixed samples, and thus ELMSI was of great value for improving the recognition effect of micro-satellite regions and supporting clinical decision supporting. The source codes have been uploaded and maintained at https://github.com/YixuanWang1120/ELMSI for academic use only.


Assuntos
Repetições de Microssatélites/genética , Neoplasias/genética , Interface Usuário-Computador , Algoritmos , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias/patologia , Polimorfismo de Nucleotídeo Único
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