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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 97-101, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950797

RESUMO

Objective: To analyse potential genetic cause of a family affected with hereditary elliptocytosis (HE). Methods: Peripheral blood samples from this HE family were collected. Targeted capture and high-throughput sequencing of 4 813 genetic disease-associated genes was performed in four members of the family. Possible causative genetic variation was obtained and further confirmed by Sanger sequencing. Fifty healthy control subjects were recruited for detection of the candidate variation. Results: High-throughput sequencing detected a nonsense mutation c.1215G>A(p.Trp405Ter)in exon 13 of the EPB41 gene in the proband and his mother presenting with moderate anemia. The pathogenicity of this loss-of-function mutation is very strong, because the G→A transition leads to introduce the premature stop codon instead of tryptophan codon at position 405, which producing a truncating protein with loss of important functional domains. This causative mutation is extremely rare in the population, and it has not yet been reported. The grandmother of the proband was heterozygous for the same mutation. Genotype-phenotype cosegregation was observed in this family. This mutation was not found in the 50 unrelated healthy controls. Conclusion: The c.1215G>A mutation of the EPB41 gene probably accounts for the disease in this HE family. This study reports a pathogenic EPB41 mutation in a Chinese HE family for the first time.


Assuntos
Proteínas do Citoesqueleto , Eliptocitose Hereditária , Proteínas de Membrana , Mutação , Proteínas do Citoesqueleto/genética , Eliptocitose Hereditária/genética , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas de Membrana/genética , Linhagem
3.
Bioinformatics ; 35(14): i183-i190, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31510687

RESUMO

MOTIVATION: De novo peptide sequencing based on tandem mass spectrometry data is the key technology of shotgun proteomics for identifying peptides without any database and assembling unknown proteins. However, owing to the low ion coverage in tandem mass spectra, the order of certain consecutive amino acids cannot be determined if all of their supporting fragment ions are missing, which results in the low precision of de novo sequencing. RESULTS: In order to solve this problem, we developed pNovo 3, which used a learning-to-rank framework to distinguish similar peptide candidates for each spectrum. Three metrics for measuring the similarity between each experimental spectrum and its corresponding theoretical spectrum were used as important features, in which the theoretical spectra can be precisely predicted by the pDeep algorithm using deep learning. On seven benchmark datasets from six diverse species, pNovo 3 recalled 29-102% more correct spectra, and the precision was 11-89% higher than three other state-of-the-art de novo sequencing algorithms. Furthermore, compared with the newly developed DeepNovo, which also used the deep learning approach, pNovo 3 still identified 21-50% more spectra on the nine datasets used in the study of DeepNovo. In summary, the deep learning and learning-to-rank techniques implemented in pNovo 3 significantly improve the precision of de novo sequencing, and such machine learning framework is worth extending to other related research fields to distinguish the similar sequences. AVAILABILITY AND IMPLEMENTATION: pNovo 3 can be freely downloaded from http://pfind.ict.ac.cn/software/pNovo/index.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
Nat Commun ; 10(1): 3404, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363125

RESUMO

We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets, 15N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.


Assuntos
Peptídeos/química , Proteoma/química , Ferramenta de Busca/métodos , Algoritmos , Animais , Bases de Dados de Proteínas , Humanos , Proteômica , Software
5.
BMC Neurol ; 19(1): 165, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315594

RESUMO

BACKGROUND: Nowadays, few surgery analysis has been reported in cases of epilepsy after viral encephalitis(VE). Herein, this study was to evaluate the efficacy of surgery and capability of stereoelectroencephalography (SEEG) in the definition of the epileptogenic zone (EZ) after VE, and also to explore the relationship between the SEEG features and the surgical outcomes. METHODS: We retrospectively analyzed 10 surgically treated patients that identified to suffer from epilepsy secondary to VE using SEEG, and investigated the SEEG features associated with surgical outcomes in these patients. Besides visual analysis, we used the epileptogenicity index (EI), a semi-quantitative and supplementary tool to evaluate the validity of SEEG in the context of VE. RESULTS: Among the 10 operated patients, 3 of them became completely seizure-free. The patients who got totally seizure free or significant improvement, the seizure onset was located either in the antero-mesial temporal structures or focal gyrus; patients who got worthwhile improvement or no improvement, the seizure started from multiple brain lobes. The number of electrodes classified as epileptogenic visually involved were closely correlated with EI positive onses.Anatomic areas defined and shown as EZ on MRI by visual assessment were also defined as epileptogenic by the EI in these cases. CONCLUSION: Apart from exploring the surgical outcome related to epilepsy after VE, we also bring insight into the relationship between the SEEG features and surgical outcome with the application of the supplementary methods.


Assuntos
Eletroencefalografia/métodos , Encefalite Viral/complicações , Epilepsia/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Eletrodos , Epilepsia/virologia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/cirurgia , Resultado do Tratamento , Adulto Jovem
6.
Anal Chem ; 91(15): 9724-9731, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31283184

RESUMO

In the past decade, tandem mass spectrometry (MS/MS)-based bottom-up proteomics has become the method of choice for analyzing post-translational modifications (PTMs) in complex mixtures. The key to the identification of the PTM-containing peptides and localization of the PTM-modified residues is to measure the similarities between the theoretical spectra and the experimental ones. An accurate prediction of the theoretical MS/MS spectra of the modified peptides will improve the similarity measurement. Here, we proposed the deep-learning-based pDeep2 model for PTMs. We used the transfer learning technique to train pDeep2, facilitating the training with a limited scale of benchmark PTM data. Using the public synthetic PTM data sets, including the synthetic phosphopeptides and 21 synthetic PTMs from ProteomeTools, we showed that the model trained by transfer learning was accurate (>80% Pearson correlation coefficients were higher than 0.9), and was significantly better than the models trained without transfer learning. We also showed that accurate prediction of the fragment ion intensities of the PTM neutral loss, for example, the phosphoric acid loss (-98 Da) of the phosphopeptide, will improve the discriminating power to distinguish the true phosphorylated residue from its adjacent candidate sites. pDeep2 is available at https://github.com/pFindStudio/pDeep/tree/master/pDeep2 .

7.
J Proteome Res ; 18(7): 2747-2758, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31244209

RESUMO

As the de facto validation method in mass spectrometry-based proteomics, the target-decoy approach determines a threshold to estimate the false discovery rate and then filters those identifications beyond the threshold. However, the incorrect identifications within the threshold are still unknown and further validation methods are needed. In this study, we characterized a framework of validation and investigated a number of common and novel validation methods. We first defined the accuracy of a validation method by its false-positive rate (FPR) and false-negative rate (FNR) and, further, proved that a validation method with lower FPR and FNR led to identifications with higher sensitivity and precision. Then we proposed a validation method named pValid that incorporated an open database search and a theoretical spectrum prediction strategy via a machine-learning technology. pValid was compared with four common validation methods as well as a synthetic peptide validation method. Tests on three benchmark data sets indicated that pValid had an FPR of 0.03% and an FNR of 1.79% on average, both superior to the other four common validation methods. Tests on a synthetic peptide data set also indicated that the FPR and FNR of pValid were better than those of the synthetic peptide validation method. Tests on a large-scale human proteome data set indicated that pValid successfully flagged the highest number of incorrect identifications among all five methods. Further considering its cost-effectiveness, pValid has the potential to be a feasible validation tool for peptide identification.

8.
J Cardiovasc Pharmacol ; 73(5): 265-271, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31082959

RESUMO

Emulsified isoflurane (EI) has been shown to alleviate myocardial ischemia-reperfusion (IR) injury. However, previous reports have not been focused on the underlying mechanism. We used models of IR injury in Langendorff-isolated rat hearts to determine the relationship between the mechanism underlying EI postconditioning (EIP)-induced activation of the nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element signaling pathway during myocardial IR, and its relationship with reactive oxygen species. In comparison with the IR group, the EIP group showed a significant reduction in myocardial ultrastructural damage, significant increase in function [heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rate of the increase in left ventricular pressure (+dp/dtmax)], and upregulated expression of Nrf2, HO-I, NQO1, and SOD1 mRNA and proteins at the end of reperfusion. After treatment with N-(2-mercaptopropionyl)-glycine (MPG), the significant reduction in myocardial ultrastructural damage and significant increases in function, and mRNA and protein expression were no longer evident in the M + EIP group. These results show that EIP can regulate reactive oxygen species levels and activate the Nrf2-antioxidant response element signaling pathway, thereby attenuating myocardial IR injury in rats.

9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 234-240, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106546

RESUMO

OBJECTIVE: To screen the genes with significant changes in DNA methylation level in active tuberculosis patients, we used the methylation chips and expanded the sample size to verify candidate genes. METHODS: ① This study enrolled 9 cases of active tuberculosis patients, 3 cases of latent tuberculosis patients and 3 cases of healthy controls whose age and gender were all matched. Genome DNA was extracted from peripheral blood mononuclear cell in blood samples collected from these candidates, and bisulfite conversion treatment was then conducted. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, and GO and KEGG pathway analyses were performed to evaluate the function of differentially expressed genes. ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (age-and gender-matched), DNA was extracted from their peripheral blood and also followed bisulfite conversion treatment. Pyrosequencing method was used to detect the methylation levels of candidate genes (IFNGR2, PTPN6, CRK1, ATP6V0B, WIF1, DKK1 and SFRP1) screened by gene chip. RESULTS: Compared with healthy controls, the fragments in the patients that showed low methylation change accounted for the vast majority. Most of the methylation differential fragments (DMRs) were located in the main body region, followed by the upstream region of transcription initiation site, and the lowest DMRs distribution area was 3´UTR area. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes are mainly enriched in the biological processes of the regulation of leukocyte differentiation, apoptosis, cytokine regulation and inflammatory response which are closely related to tuberculosis. There were 32 CpG sites involved in the verified 7 tuberculosis related genes, and 16 CpG locus showed significant difference (P<0.05), they were distributed in 6 genes: PTPN6, WIF1, CRK1, SFRP1, DKK1 and IFNGR2.Of these genes with significant difference, PTPN6 genes showed hypermethylation status and WIF1, CRK1, SFRP1, DKK1 and IFNGR2 genes exhibited demethylation status in the patients group compared to the health controls. SFRP1 and CRK-1 mRNA up-regulated in the patients group compared with health controls. CONCLUSION: In the course of MTB infection, the methylation status of genomic DNA is altered, and most of the differentially methylated regions (DMRs) are showed status of demethylation. The expressions ofSFRP1and CRK-1gene up-regulate in tuberculosis infection.


Assuntos
Metilação de DNA , Tuberculose Latente/genética , Análise de Sequência com Séries de Oligonucleotídeos , Tuberculose/genética , Ilhas de CpG , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leucócitos Mononucleares , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-crk/genética
10.
Psychiatry Clin Neurosci ; 73(3): 109-115, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30375100

RESUMO

AIM: Although peripheral low-grade inflammation and brain-derived neurotrophic factor (BDNF) levels have been implicated in schizophrenia (SCZ), the interactions between them remain to be fully revealed. We aimed to compare BDNF and cytokines in patients with SCZ and healthy controls (HC). Additionally, we aimed to investigate the association between peripheral levels of cytokines and BDNF in patients with SCZ. METHODS: Plasma levels of BDNF, interferon gamma, interleukin (IL)-10, IL-12, IL-1, IL-6, IL-8, tumor necrosis factor alpha, macrophage migration inhibitory factor, IL-1 receptor antagonist (IL-1Ra), and CD40 Ligand were compared in 45 SCZ patients and 38 HC using Luminex technology. RESULTS: Compared to HC, patients had significantly higher IL-1Ra levels (P = 0.031). We found a strong positive association between BDNF and CD40 Ligand in the patient group (rho = 0.858, P < 0.001) as well as in the HC group (rho = 0.822, P < 0.001), respectively. Furthermore, there was a negative association between BDNF and tumor necrosis factor alpha in patients (rho = -0.429, P = 0.030) as well as in HC (rho = -0.649, P < 0.001). CONCLUSION: These results suggest that the cytokine IL-1Ra may play a role in SCZ pathophysiology. Additionally, the interaction between cytokines and BDNF levels further indicated the diverse actions of these cytokines.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Citocinas/sangue , Proteína Antagonista do Receptor de Interleucina 1/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Adulto Jovem
11.
Nat Biotechnol ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30295672

RESUMO

We present a sequence-tag-based search engine, Open-pFind, to identify peptides in an ultra-large search space that includes coeluting peptides, unexpected modifications and digestions. Our method detects peptides with higher precision and speed than seven other search engines. Open-pFind identified 70-85% of the tandem mass spectra in four large-scale datasets and 14,064 proteins, each supported by at least two protein-unique peptides, in a human proteome dataset.

12.
Ecotoxicol Environ Saf ; 157: 61-66, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29605644

RESUMO

Nine antialgal active compounds, (i.e. trehalose (1), twenty-two methyl carbonate (2), (-)-dihydromenisdaurilide (3), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (4), isophytol (5), 8-hexadecenol (6), 17-hydroxyheptadecanoic acid (7), trans-asarone (8) and 2-amino-3-mercaptopropanoic acid (9)) were isolated from Ulva pertusa for the first time by sephadex LH-20 column chromatography, silica gel column chromatography and repeated preparative TLC. Except for compound 4, all compounds represented novel isolated molecules from marine macroalgae. Further, antialgal activities of these compounds against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense and Skeletonema costatum were investigated for the first time. Results showed these nine compounds have selectivity antialgal effects on all test red tide microalgae, and antialgal activities against red tide microalgae obviously enhanced with the increase of concentration of antialgal compounds. Based on this, EC50-96 h values of these nine compounds for six red tide microalgae were obtained for the first time. By analyzing and comparing EC50-96 h values, it has been determined that seven compounds (1, 3, 4, 6, 7, 8 and 9) showed the superior application potential than potassium dichromate or gossonorol and other six compounds as a characteristic antialgal agent against Heterosigma akashiwo, Karenia mikimitoi and Prorocentrum donghaiense. Overall this study has suggested that green algae Ulva pertusa is a new source of bioactive compounds with antialgal activity.


Assuntos
Microalgas/efeitos dos fármacos , Ulva/química , Diatomáceas/efeitos dos fármacos , Dinoflagelados/efeitos dos fármacos , Haptófitas/efeitos dos fármacos , Proliferação Nociva de Algas , Estramenópilas/efeitos dos fármacos
13.
Appl Opt ; 57(1): A222-A228, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29328149

RESUMO

A finite difference method is proposed for solving the transport of intensity equation. Simulation results show that although slower than fast Fourier transform (FFT)-based methods, finite difference methods are able to reconstruct the phase with better accuracy due to relaxed assumptions for solving the transport of intensity equation relative to FFT methods. Finite difference methods are also more flexible than FFT methods in dealing with different boundary conditions.

14.
Appl Opt ; 57(1): A229-A234, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29328150

RESUMO

We propose a technique in which intensity images are reconstructed from a digital hologram to provide inputs for the transport-of-intensity equation for unwrapped phase recovery. By doing this, we avoid shifting of the sample or the camera in the experiment, a method commonly employed while using the method of transport-of-intensity equation for phase retrieval. Computer simulations as well as experimental results have been demonstrated to verify the effectiveness of the proposed idea. The underlying numerical technique can also be viewed as an alternative to existing phase-unwrapping algorithms.

15.
Environ Sci Pollut Res Int ; 25(8): 7844-7859, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29297163

RESUMO

Previous studies showed that methanol extracts from Porphyra yezoensis significantly inhibited Karenia mikimitoi and Skeletonema costatum. Five sesquiterpenoids (1-5) were successfully isolated from this marine macroalga through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography in this paper. Their structure was identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), cyclonerodiol (3), cadinol, (4) and 4-cadinen-1-ol (5) on the basis of spectroscopic data. These sesquiterpenoids were isolated from Porphyra yezoensis for the first time, and cyclonerodiol (3) and cadinol (4) isolated from marine macroalgae for the first time. Further, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal sesquiterpenoid (gossonorol, 7,10-epoxy-ar-bisabol-11-ol and cyclonerodiol) was determined and important parameters, e.g., EC50-96h for future practical HAB control are to be obtained. Results showed that three sesquiterpenoids (1-3) had selective antialgal activity against the growth of red tide microalgae (Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense, and Skeletonema costatum). More than two test red tide microalgae were significantly inhibited by these three sesquiterpenoids (1-3). Their antialgal activity against red tide microalgae has not been previously reported. Furthermore, EC50-96h of gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) for specific test red microalgae were not only significantly less than 10 µg/mL, but also were smaller than/or very close to those of potassium dichromate. Gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) possessed good application potential than potassium dichromate as a characteristic antialgal agent against the specific harmful red tide microalgae (Heterosigma akashiwo, Phaeocystis globosa, and Prorocentrum donghaiense) (or Heterosigma akashiwo and Karenia mikimitoi).


Assuntos
Proliferação Nociva de Algas , Herbicidas/farmacologia , Microalgas/efeitos dos fármacos , Porphyra/química , Alga Marinha/química , Sesquiterpenos/farmacologia , Organismos Aquáticos/efeitos dos fármacos , Herbicidas/química , Microalgas/crescimento & desenvolvimento , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
16.
J Proteome Res ; 17(1): 119-128, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29130300

RESUMO

MS-based de novo peptide sequencing has been improved remarkably with significant development of mass-spectrometry and computational approaches but still lacks quality-control methods. Here we proposed a novel algorithm pSite to evaluate the confidence of each amino acid rather than the full-length peptides obtained by de novo peptide sequencing. A semi-supervised learning approach was used to discriminate correct amino acids from random one; then, an expectation-maximization algorithm was used to adaptively control the false amino-acid rate (FAR). On three test data sets, pSite recalled 86% more amino acids on average than PEAKS at the FAR of 5%. pSite also performed superiorly on the modification site localization problem, which is essentially a special case of amino acid confidence evaluation. On three phosphopeptide data sets, at the false localization rate of 1%, the average recall of pSite was 91% while those of Ascore and phosphoRS were 64 and 63%, respectively. pSite covered 98% of Ascore and phosphoRS results and contributed 21% more phosphorylation sites. Further analyses show that the use of distinct fragmentation features in high-resolution MS/MS spectra, such as neutral loss ions, played an important role in improving the precision of pSite. In summary, the effective and universal model together with the extensive use of spectral information makes pSite an excellent quality control tool for both de novo peptide sequencing and modification site localization.


Assuntos
Sítios de Ligação , Processamento de Proteína Pós-Traducional , Análise de Sequência de Proteína/métodos , Espectrometria de Massas em Tandem/métodos , Algoritmos , Aminoácidos , Fosforilação , Controle de Qualidade
17.
Epilepsia ; 58(10): 1697-1705, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28833053

RESUMO

OBJECTIVE: In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD. METHODS: We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files. RESULTS: Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years. SIGNIFICANCE: Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.


Assuntos
Epilepsia/patologia , Malformações do Desenvolvimento Cortical/patologia , Lobo Occipital/patologia , Adolescente , Criança , Epilepsia/classificação , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Feminino , Humanos , Hipóxia-Isquemia Encefálica , Imagem por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Lobo Occipital/cirurgia , Estudos Retrospectivos , Adulto Jovem
18.
J Proteome Res ; 16(2): 645-654, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28019094

RESUMO

De novo peptide sequencing has improved remarkably, but sequencing full-length peptides with unexpected modifications is still a challenging problem. Here we present an open de novo sequencing tool, Open-pNovo, for de novo sequencing of peptides with arbitrary types of modifications. Although the search space increases by ∼300 times, Open-pNovo is close to or even ∼10-times faster than the other three proposed algorithms. Furthermore, considering top-1 candidates on three MS/MS data sets, Open-pNovo can recall over 90% of the results obtained by any one traditional algorithm and report 5-87% more peptides, including 14-250% more modified peptides. On a high-quality simulated data set, ∼85% peptides with arbitrary modifications can be recalled by Open-pNovo, while hardly any results can be recalled by others. In summary, Open-pNovo is an excellent tool for open de novo sequencing and has great potential for discovering unexpected modifications in the real biological applications.


Assuntos
Sequência de Aminoácidos/genética , Peptídeos/genética , Processamento de Proteína Pós-Traducional/genética , Algoritmos , Bases de Dados de Proteínas , Análise de Sequência de Proteína , Software , Espectrometria de Massas em Tandem
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(6): 920-925, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28598125

RESUMO

OBJECTIVES: To determine the correlation between gene polymorphisms in Wnt signal pathway and susceptibility of Chinese Tibetan people to tuberculosis. METHODS: A total of 488 active tuberculosis patients and 454 healthy subjects(control) were enrolled in this case-control study.Five single nucleotide polymorphisms (SNPs) in Wnt signal pathway (rs4135385 in CTNNB1 gene,rs11001553 in DKK1 gene,rs56900803 in WIF1 gene,rs7832767 in SFRP1 gene and rs11079571 in AXIN2 gene) were genotyped using MassARRAY method.The genotype and allele distributions of these loci were determined using SPSS19.0 and SNP stats software.Significant SNPs were measured in the co-dominant,dominant and recessive genetic models.The polymorphism distributions of Chinese Tibetans were compared with those of Chinese Han populations. RESULTS: The genotype distributions of all SNPs coincided with the Hardy-Weinberg equilibrium in the 2 groups.The frequencies of genotype and allele of rs7832767 in SFRP1 gene were significantly different (P=0.004,0.002,respectively) between the Tibetan patients with tuberculosis and the Tibetan healthy controls.Compared with C allele carriers,those carrying T allele of rs7832767 showed increased risk of tuberculosis [odds ratio (OR)=1.260,95% confidence interval (CI):1.086-1.471,P=0.002].The co-dominant,dominant and recessive models of this locus were also associated with higher risk of tuberculosis.No significant differences in genotype and allele distributions were observed for the other four SNP loci (P all>0.05).The distribution of rs4135385 in CTNNB1 gene in the Chinese Tibetan population differed from the Han population (P=0.035 for genotype,0.021 for allele).There were no obvious differences in genotype and allele distributions for the other four SNPs between the Tibetan and Han populations (P all >0.05). CONCLUSIONS: SFRP1 gene polymorphism in Wnt signal pathway is associated with tuberculosis susceptibility in Chinese Tibetan population.The distribution of CTNNB1 gene polymorphism differs between Chinese Tibetan and Han populations.


Assuntos
Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Via de Sinalização Wnt/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Proteína Axina/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas Repressoras/genética , Tibet , beta Catenina/genética
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(6): 936-940, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28598128

RESUMO

OBJECTIVES: To investigate the molecular features of spinal muscular atrophy (SMA) related genes in SMA patients of Han nationality of southwest of China. METHODS: We collected 62 unrelated patients of SMA and 50 unrelated healthy individuals in this study.The copy numbers of survival motor neuron gene (SMN) and uronal-apoptosis inhibitory protein gene (NAIP) were measured by using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Of 62 patients,the copy number of SMA1-4 were 30.65% (19/62),41.94%(26/62),16.13% (10/62),11.29% (7/62),respectively.The deletion of SMN1 exon 7 accounts for 98.38% (61/62).The deletion of SMN1 exon 8 accounts for 82.26% (51/62).Among SMA 1 patients,the homozygous deletion of NAIP exon 5 accounts for 68.42% (13/19) and heterzygous deletion accounts for 26.32% (5/19).Among SMA2-4patients,the homozygous deletion of NAIP exon 5 accounts for 13.95% (6/43) and heterzygous deletion accounts for 62.79% (27/43).Furthermore,68.42% (13/19) patients of SMA1have 1 copy and 2 copies of SMN2 gene,84.62% (22/26) patients of SMA 2 have more than 2 copies of SMN2 gene,90.00% (9/10) SMA3 and 85.71% (6/7) SMA4 have over 2 copies of SMN2 gene and even have 5 and 6 copy of SMN2 gene. CONCLUSIONS: The deletion of SMN1 gene is the main cause of SMA,and the change of SMN2 and NAIP copy number can affect the severity of SMA.


Assuntos
Atrofia Muscular Espinal/genética , Proteína Inibidora de Apoptose Neuronal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , China , Grupos Étnicos , Éxons , Deleção de Genes , Dosagem de Genes , Humanos , Proteínas de Ligação a RNA
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