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1.
Sensors (Basel) ; 24(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38475003

RESUMO

Cracks are common defects that occur on the surfaces of objects and structures. Crack detection is a critical maintenance task that traditionally requires manual labor. Large-scale manual inspections are expensive. Research has been conducted to replace expensive human labor with cheaper computing resources. Recently, crack segmentation based on convolutional neural networks (CNNs) and transformers has been actively investigated for local and global information. However, the transformer is data-intensive owing to its weak inductive bias. Existing labeled datasets for crack segmentation are relatively small. Additionally, a limited amount of fine-grained crack data is available. To address this data-intensive problem, we propose a parallel dual encoder network fusing Pre-Conv-based Transformers and convolutional neural networks (PCTC-Net). The Pre-Conv module automatically optimizes each color channel with a small spatial kernel before the input of the transformer. The proposed model, PCTC-Net, was tested with the DeepCrack, Crack500, and Crackseg9k datasets. The experimental results showed that our model achieved higher generalization performance, stability, and F1 scores than the SOTA model DTrC-Net.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38420727

RESUMO

BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.

3.
BMB Rep ; 57(2): 110-115, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37605617

RESUMO

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the thylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC. [BMB Reports 2024; 57(2): 110-115].


Assuntos
Neoplasias Colorretais , Metilação de DNA , Humanos , Metilação de DNA/genética , Instabilidade de Microssatélites , Mutação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , República da Coreia , Ilhas de CpG/genética , Fenótipo
4.
ACS Appl Mater Interfaces ; 15(51): 59939-59945, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38087433

RESUMO

Electrochemical torsional artificial muscles have the potential to replace electric motors in the field of miniaturization. In particular, carbon nanotubes (CNTs) are some of the best materials for electrochemical torsional artificial muscles due to their remarkable mechanical strength and high electrical conductivity. However, previous studies on CNT torsional muscle utilize only half of the whole potential range for torsional actuation because the actuations in the positive and negative voltage ranges offset each other. Here, we used an ion-exchange polymer, poly(sodium 4-styrenesulfonate) (PSS), which leads to the participation of only positive ions in the actuation of CNT muscles so that the whole potential range can be used for torsional actuation. As a result, PSS-coated CNT muscle can provide 1.9 times higher torsional actuation compared to neat CNT torsional muscle. This PSS-coated CNT muscle not only provides high performance but also facilitates a one-body system for electrochemical torsional actuation. From these advantages, we implement a one-body torsional muscle for the realization of the forward motion of a model boat. This high performance and one-body structure for electrochemical torsional muscles can be used for further applications, such as soft robotics and implantable devices.

5.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139162

RESUMO

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by epidermal barrier dysfunction and Th2-skewed inflammation. Campanula takesimana (C. takesimana), a Korean endemic plant grown on Ulleng Island, has long been associated with a traditional alternative medicine for asthma, tonsillitis, and sore throat. In this study, we reported the effect of C. takesimana callus extract on upregulating epidermal barrier-related proteins dysregulated by Th2 cytokines. C. takesimana callus extract induced the expression of skin barrier proteins, such as filaggrin, claudin-1, and zonula occludens-1, in both human primary keratinocytes and Th2-induced AD-like skin-equivalent models. Additionally, RNA sequencing analysis demonstrated that C. takesimana callus extract partially restored Th2 cytokine-induced dysregulation of the epidermal development and lipid metabolic pathways. Considering the advantages of callus as a sustainable eco-friendly source of bioactive substances, and its effect on skin barrier proteins and lipid metabolic pathways, C. takesimana callus extracts can possibly be utilized to improve the integrity of the skin barrier.


Assuntos
Dermatite Atópica , Pele , Humanos , Pele/metabolismo , Dermatite Atópica/metabolismo , Queratinócitos/metabolismo , Citocinas/metabolismo , Lipídeos/farmacologia
6.
Res Sq ; 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37398410

RESUMO

Single allelic mutations in the gene encoding the forebrain-specific transcription factor FOXG1 lead to FOXG1 syndrome (FS). Patient-specific animal models are needed to understand the etiology of FS, as FS patients show a wide spectrum of symptoms correlated with location and mutation type in the FOXG1 gene. Here we report the first patient-specific FS mouse model, Q84Pfs heterozygous (Q84Pfs-Het) mice, mimicking one of the most predominant single nucleotide variants in FS. Intriguingly, we found that Q84Pfs-Het mice faithfully recapitulate human FS phenotypes at the cellular, brain structural, and behavioral levels. Importantly, Q84Pfs-Het mice exhibited myelination deficits like FS patients. Further, our transcriptome analysis of Q84Pfs-Het cortex revealed a new role for FOXG1 in synapse and oligodendrocyte development. The dysregulated genes in Q84Pfs-Het brains also predicted motor dysfunction and autism-like phenotypes. Correspondingly, Q84Pfs-Het mice showed movement deficits, repetitive behaviors, increased anxiety, and prolonged behavior arrest. Together, our study revealed the crucial postnatal role of FOXG1 in neuronal maturation and myelination and elucidated the essential pathophysiology mechanisms of FS.

7.
Small Methods ; 7(10): e2300526, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37317005

RESUMO

Owing to increasing amount of research on energy harvesting, studies on harvesters for practical application and their performance are attracting attention. Therefore, studies on the use of continuous energy as an energy source for energy-harvesting devices are being conducted, and fluid flows, e.g., wind, river flow, and sea wave, are widely used as input energy sources for continuous energy harvesting. A new energy-harvesting technology has emerged based on the mechanical stretch and release of coiled carbon nanotube (CNT) yarns, which generate energy based on the change in the electrochemical double-layer capacitance. First, this CNT yarn-based mechanical energy harvester is demonstrated, which is applicable to various environments where fluid flow exists. This environment-adaptable harvester uses rotational energy as the mechanical energy source and is tested in river and ocean environments. Moreover, an attachable-type harvester for the application of the existing rotational system is devised. In the case of a slow rotational environment, a square-wave strain-applying harvester has been implemented, which can convert sinusoidal strain motion into square-wave strain motion for high output voltages. To achieve high performance of practical harvesting applications, a scale-up method for powering signal-transmitting devices has been implemented.

9.
Exp Mol Med ; 55(3): 665-679, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36964252

RESUMO

Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) are known to exert immunosuppressive functions. This study showed that MSC-sEVs specifically convert T helper 17 (Th17) cells into IL-17 low-producer (ex-Th17) cells by degrading RAR-related orphan receptor γt (RORγt) at the protein level. In experimental autoimmune encephalomyelitis (EAE)-induced mice, treatment with MSC-sEVs was found to not only ameliorate clinical symptoms but also to reduce the number of Th17 cells in draining lymph nodes and the central nervous system. MSC-sEVs were found to destabilize RORγt by K63 deubiquitination and deacetylation, which was attributed to the EP300-interacting inhibitor of differentiation 3 (Eid3) contained in the MSC-sEVs. Small extracellular vesicles isolated from the Eid3 knockdown MSCs by Eid3-shRNA failed to downregulate RORγt. Moreover, forced expression of Eid3 by gene transfection was found to significantly decrease the protein level of RORγt in Th17 cells. Altogether, this study reveals the novel immunosuppressive mechanisms of MSC-sEVs, which suggests the feasibility of MSC-sEVs as an attractive therapeutic tool for curing Th17-mediated inflammatory diseases.


Assuntos
Encefalomielite Autoimune Experimental , Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Camundongos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Células Th17 , Diferenciação Celular/genética , Processamento de Proteína Pós-Traducional , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo
10.
Adv Mater ; 35(13): e2206945, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36680462

RESUMO

For decades, group-III-nitride-based light-emitting diodes (LEDs) have been regarded as a light emitting source for future displays by virtue of their novel properties such as high efficiency, brightness, and stability. Nevertheless, realization of high pixel density displays is still challenging due to limitations of pixelation methods. Here, a maskless and etching-free micro-LED (µLED) pixelation method is developed via tailored He focused ion beam (FIB) irradiation technique, and electrically driven sub-micrometer-scale µLED pixel arrays are demonstrated. It is confirmed that optical quenching and electrical isolation effects are simultaneously induced at a certain ion dose (≈1014 ions cm-2 ) without surface damage. Furthermore, highly efficient µLED pixel arrays at sub-micrometer scale (square pixel, 0.5 µm side length) are fabricated. Their pixelation and brightness are verified by various optical measurements such as cathodo-, photo-, and electroluminescence. It is expected that the FIB-induced optical quenching and electrical isolation method can pioneer a new defect engineering technology not only for µLED fabrication, but also for sub-micrometer-scale optoelectronic devices.

11.
ACS Appl Mater Interfaces ; 14(40): 45149-45155, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36169191

RESUMO

A surface electromyogram (sEMG) electrode collects electrical currents generated by neuromuscular activity by a noninvasive technique on the skin. It is particularly attractive for wearable systems for various human activities and health care monitoring. However, it remains challenging to discriminate EMG signals from isotonic (concentric/eccentric) and isometric movements. By applying nanotechnology, we provide a coiled carbon nanotube (CNT) yarn-integrated sEMG device to overcome sEMG-based motion recognition. When the arm was contracted at different angles, the sEMG-derived root mean square amplitude signals were constant regardless of the angle of the moving arm. However, the coiled CNT yarn-derived open circuit voltage (OCV) signals proportionally increased when the arm's angle increased, and presented negative and positive values depending on the moving direction of the arm. Moreover, isometric contraction is characterized by the onset of EMG signals without an OCV signal, and isotonic contraction is determined by both EMG signals and OCV signals. Taken together, the integration of EMG and coiled CNT yarn electrodes provides complementary information, including the strength, direction, and degree of muscle movement. Therefore, we suggest that our system has high potential as a wearable system to monitor human motions in industrial and human system applications.


Assuntos
Nanotubos de Carbono , Eletromiografia , Humanos , Contração Isométrica/fisiologia , Movimento , Músculo Esquelético/fisiologia
12.
Adv Mater ; 34(27): e2201826, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35475584

RESUMO

Stretching a coiled carbon nanotube (CNT) yarn can provide large, reversible electrochemical capacitance changes, which convert mechanical energy to electricity. Here, it is shown that the performance of these "twistron" harvesters can be increased by optimizing the alignment of precursor CNT forests, plastically stretching the precursor twisted yarn, applying much higher tensile loads during precoiling twist than for coiling, using electrothermal pulse annealing under tension, and incorporating reduced graphene oxide nanoplates. The peak output power for a 1 and a 30 Hz sinusoidal deformation are 0.73 and 3.19 kW kg-1 , respectively, which are 24- and 13-fold that of previous twistron harvesters at these respective frequencies. This performance at 30 Hz is over 12-fold that of other prior-art mechanical energy harvesters for frequencies between 0.1 and 600 Hz. The maximum energy conversion efficiency is 7.2-fold that for previous twistrons. Twistron anode and cathode yarn arrays are stretched 180° out-of-phase by locating them in the negative and positive compressibility directions of hinged wine-rack frames, thereby doubling the output voltage and reducing the input mechanical energy.

13.
IEEE/ACM Trans Comput Biol Bioinform ; 19(4): 2356-2364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33750713

RESUMO

MOTIVATION: Identifying differentially expressed genes (DEGs) in transcriptome data is a very important task. However, performances of existing DEG methods vary significantly for data sets measured in different conditions and no single statistical or machine learning model for DEG detection perform consistently well for data sets of different traits. In addition, setting a cutoff value for the significance of differential expressions is one of confounding factors to determine DEGs. RESULTS: We address these problems by developing an ensemble model that refines the heterogeneous and inconsistent results of the existing methods by taking accounts into network information such as network propagation and network property. DEG candidates that are predicted with weak evidence by the existing tools are re-classified by our proposed ensemble model for the transcriptome data. Tested on 10 RNA-seq datasets downloaded from gene expression omnibus (GEO), our method showed excellent performance of winning the first place in detecting ground truth (GT) genes in eight datasets and find almost all GT genes in six datasets. On the other hand, performances of all existing methods varied significantly for the 10 data sets. Because of the design principle, our method can accommodate any new DEG methods naturally. AVAILABILITY: The source code of our method is available at https://github.com/jihmoon/MLDEG.


Assuntos
Perfilação da Expressão Gênica , Software , Perfilação da Expressão Gênica/métodos , Aprendizado de Máquina , Transcriptoma
14.
Acute Crit Care ; 36(1): 70-74, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33040519

RESUMO

Acute pericarditis is caused by various factors, but purulent pericarditis is rare. Primary purulent pericarditis in immunocompetent hosts is very rare in the modern antibiotics era. We report a successfully treated case of primary purulent pericarditis complicated with cardiac tamponade and pneumopericardium in an immunocompetent host. A 69-year-old female was referred from another hospital because of pleuritic chest pain with a large amount of pericardial effusion. She was diagnosed with acute pericarditis accompanied by cardiac tamponade. We performed emergency pericardiocentesis, with drainage of 360 ml of bloody pericardial fluid. The culture grew Streptococcus anginosus, confirming the diagnosis of acute purulent pericarditis. We performed pericardiostomy because cardiomegaly and pneumopericardium were aggravated after removal of the pericardial drainage catheter. The patient received antibiotics for a total of 23 days intravenously and was discharged with oral antibiotic therapy. Purulent pericarditis is one of the rare forms of pericarditis and is lifethreatening. A multimodality approach is required for proper diagnosis and treatment of this disease.

15.
ACS Appl Mater Interfaces ; 12(41): 46883-46891, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32931230

RESUMO

Thin and flexible electromagnetic shielding materials have recently emerged because of their promising applications in drones, portable electronics, military defense facilities, etc. This research develops an electromagnetic interference (EMI) shielding material by a bidirectional lattice sandwich structure (BLSS), which is formed by liquid crystalline graphene oxide (LCGO) and an orthogonal pattern of spinnable multiwalled (OPSM) nanotubes in consideration of the movement of electromagnetic waves. The average EMI shielding effectiveness (SE) of the developed material with 0.5 wt % reduced LCGO (r-LCGO) and an OPSM nanotube composed of 64 layers was approximately 66.1 dB in the X-band frequency range (8.2-12.4 GHz, wavelength: 3.5-2.5 cm), which corresponds to a shielding efficiency of 99.9999%. Also, its absorption effectiveness is 99.7% of the total EMI SE, indicating that it has a remarkable ability to prevent secondary damage induced by EM reflection. The specific EMI SE (SSE/t) of the composite material considering the contribution of thickness (t) ranged from 21 953 to 2259 dB cm2/g.

16.
Cell Rep ; 32(11): 108147, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32937136

RESUMO

PRC2 creates the repressive mark histone H3 Lys27 trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. Here, we show that PRC2 is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. PRC2-deficient OL lineage cells differentiate into OL precursors, but they fail to trigger the molecular program for myelination, highlighting that PRC2 is essential for directing the differentiation timing of OL precursors. PRC2 null OL lineage cells aberrantly induce Notch pathway genes and acquire astrocytic features. The repression of the Notch pathway restores the myelination program and inhibits abnormal astrocytic differentiation in the PRC2-deficient OL lineage, indicating that Notch is a major target of PRC2. Altogether, our studies propose a specific action of PRC2 as a novel gatekeeper that determines the glial fate choice and the timing of OL lineage progression and myelination by impinging on the Notch pathway.


Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Linhagem da Célula , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Diferenciação Celular , Galinhas , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Metilação , Camundongos , Bainha de Mielina/metabolismo , Fatores de Transcrição NFI/metabolismo , Medula Espinal/citologia , Medula Espinal/ultraestrutura , Células-Tronco/citologia , Células-Tronco/metabolismo , Via de Sinalização Wnt
17.
Immunol Lett ; 225: 16-22, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32554049

RESUMO

Mouse mesenchymal stem cells (MSCs) have been shown to suppress T cells. Especially, MSC-cultured media have shown suppressive functions against various immune cells including the T cells. However, the underlying immunosuppressive mechanisms of the MSC-cultured medium are not yet fully understood. In this study, we confirmed the T cell-suppression capacity of MSC culture supernatant (MSC-CS) through both apoptosis and cell cycle arrest, and hypothesized that the exosomes were the major immunosuppressive agents in the MSC-CS. MSC-derived exosomes (MSC-exo) exhibited potent suppressive effects on T cell proliferation while the rest of the supernatant fraction did not. Interestingly, the exosomes derived from MSC only induced the cell cycle arrest, and it was through the upregulation of p27kip1 protein and downregulation of Cdk2 protein. In conclusion, the exosomes secreted from MSCs could suppress the activated T cell proliferation through the induction of cell cycle arrest.


Assuntos
Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Exossomos/metabolismo , Células-Tronco Mesenquimais/fisiologia , Linfócitos T/imunologia , Animais , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Células Cultivadas , Feminino , Tolerância Imunológica , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
18.
BMC Med Genomics ; 13(Suppl 3): 27, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093698

RESUMO

BACKGROUND: In cancer, mutations of DNA methylation modification genes have crucial roles for epigenetic modifications genome-wide, which lead to the activation or suppression of important genes including tumor suppressor genes. Mutations on the epigenetic modifiers could affect the enzyme activity, which would result in the difference in genome-wide methylation profiles and, activation of downstream genes. Therefore, we investigated the effect of mutations on DNA methylation modification genes such as DNMT1, DNMT3A, MBD1, MBD4, TET1, TET2 and TET3 through a pan-cancer analysis. METHODS: First, we investigated the effect of mutations in DNA methylation modification genes on genome-wide methylation profiles. We collected 3,644 samples that have both of mRNA and methylation data from 12 major cancer types in The Cancer Genome Atlas (TCGA). The samples were divided into two groups according to the mutational signature. Differentially methylated regions (DMR) that overlapped with the promoter region were selected using minfi and differentially expressed genes (DEG) were identified using EBSeq. By integrating the DMR and DEG results, we constructed a comprehensive DNA methylome profiles on a pan-cancer scale. Second, we investigated the effect of DNA methylations in the promoter regions on downstream genes by comparing the two groups of samples in 11 cancer types. To investigate the effects of promoter methylation on downstream gene activations, we performed clustering analysis of DEGs. Among the DEGs, we selected highly correlated gene set that had differentially methylated promoter regions using graph based sub-network clustering methods. RESULTS: We chose an up-regulated DEGs cluster where had hypomethylated promoter in acute myeloid leukemia (LAML) and another down-regulated DEGs cluster where had hypermethylated promoter in colon adenocarcinoma (COAD). To rule out effects of gene regulation by transcription factor (TF), if differentially expressed TFs bound to the promoter of DEGs, that DEGs did not included to the gene set that effected by DNA methylation modifiers. Consequently, we identified 54 hypomethylated promoter DMR up-regulated DEGs in LAML and 45 hypermethylated promoter DMR down-regulated DEGs in COAD. CONCLUSIONS: Our study on DNA methylation modification genes in mutated vs. non-mutated groups could provide useful insight into the epigenetic regulation of DEGs in cancer.


Assuntos
Metilação de DNA/genética , DNA de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Epigênese Genética , Epigenoma , Genoma Humano , Humanos , Mutação , Regiões Promotoras Genéticas
19.
Sci Rep ; 9(1): 18835, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827198

RESUMO

Clinical islet transplantation has recently been a promising treatment option for intractable type 1 diabetes patients. Although early graft loss has been well studied and controlled, the mechanisms of late graft loss largely remains obscure. Since long-term islet graft survival had not been achieved in islet xenotransplantation, it has been impossible to explore the mechanism of late islet graft loss. Fortunately, recent advances where consistent long-term survival (≥6 months) of adult porcine islet grafts was achieved in five independent, diabetic nonhuman primates (NHPs) enabled us to investigate on the late graft loss. Regardless of the conventional immune monitoring methods applied in the post-transplant period, the initiation of late graft loss could rarely be detected before the overt graft loss observed via uncontrolled blood glucose level. Thus, we retrospectively analyzed the gene expression profiles in 2 rhesus monkey recipients using peripheral blood RNA-sequencing (RNA-seq) data to find out the potential cause(s) of late graft loss. Bioinformatic analyses showed that highly relevant immunological pathways were activated in the animal which experienced late graft failure. Further connectivity analyses revealed that the activation of T cell signaling pathways was the most prominent, suggesting that T cell-mediated graft rejection could be the cause of the late-phase islet loss. Indeed, the porcine islets in the biopsied monkey liver samples were heavily infiltrated with CD3+ T cells. Furthermore, hypothesis test using a computational experiment reinforced our conclusion. Taken together, we suggest that bioinformatics analyses with peripheral blood RNA-seq could unveil the cause of insidious late islet graft loss.


Assuntos
Rejeição de Enxerto/genética , Hiperglicemia/cirurgia , Transplante das Ilhotas Pancreáticas , Macaca mulatta/cirurgia , RNA , Sus scrofa , Animais , Biologia Computacional , Regulação da Expressão Gênica , Rejeição de Enxerto/sangue , Macaca mulatta/genética , Macaca mulatta/imunologia , RNA/sangue , RNA/genética , Análise de Sequência de RNA , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Heterólogo
20.
BMC Bioinformatics ; 20(Suppl 23): 667, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881980

RESUMO

BACKGROUND: The main research topic in this paper is how to compare multiple biological experiments using transcriptome data, where each experiment is measured and designed to compare control and treated samples. Comparison of multiple biological experiments is usually performed in terms of the number of DEGs in an arbitrary combination of biological experiments. This process is usually facilitated with Venn diagram but there are several issues when Venn diagram is used to compare and analyze multiple experiments in terms of DEGs. First, current Venn diagram tools do not provide systematic analysis to prioritize genes. Because that current tools generally do not fully focus to prioritize genes, genes that are located in the segments in the Venn diagram (especially, intersection) is usually difficult to rank. Second, elucidating the phenotypic difference only with the lists of DEGs and expression values is challenging when the experimental designs have the combination of treatments. Experiment designs that aim to find the synergistic effect of the combination of treatments are very difficult to find without an informative system. RESULTS: We introduce Venn-diaNet, a Venn diagram based analysis framework that uses network propagation upon protein-protein interaction network to prioritizes genes from experiments that have multiple DEG lists. We suggest that the two issues can be effectively handled by ranking or prioritizing genes with segments of a Venn diagram. The user can easily compare multiple DEG lists with gene rankings, which is easy to understand and also can be coupled with additional analysis for their purposes. Our system provides a web-based interface to select seed genes in any of areas in a Venn diagram and then perform network propagation analysis to measure the influence of the selected seed genes in terms of ranked list of DEGs. CONCLUSIONS: We suggest that our system can logically guide to select seed genes without additional prior knowledge that makes us free from the seed selection of network propagation issues. We showed that Venn-diaNet can reproduce the research findings reported in the original papers that have experiments that compare two, three and eight experiments. Venn-diaNet is freely available at: http://biohealth.snu.ac.kr/software/venndianet.


Assuntos
Redes Reguladoras de Genes , Software , Animais , Perfilação da Expressão Gênica , Ontologia Genética , Internet , Camundongos Knockout , Mapas de Interação de Proteínas , Transcriptoma , Interface Usuário-Computador
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