LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 1457

Search options

  1. Article ; Online: Deep learning program to predict protein functions based on sequence information

    Chang Woo Ko / June Huh / Jong-Wan Park

    MethodsX, Vol 9, Iss , Pp 101622- (2022)

    2022  

    Abstract: Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We ... ...

    Abstract Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We designed a binary classification deep learning program requiring only sequence information. This program was named ‘FUTUSA’ (function teller using sequence alone). It applied sequence segmentation during the sequence feature extraction process, by a convolution neural network, to train the regional sequence patterns and their relationship. This segmentation process improved the predictive performance by 49% than the full-length process. Compared with a baseline method, our approach achieved higher performance in predicting oxidoreductase activity. In addition, FUTUSA also showed dramatic performance in predicting acetyltransferase and demethylase activities. Next, we tested the possibility that FUTUSA can predict the functional consequence of point mutation. After trained for monooxygenase activity, FUTUSA successfully predicted the impact of point mutations on phenylalanine hydroxylase, which is responsible for an inherited metabolic disease PKU. This deep-learning program can be used as the first-step tool for characterizing newly identified or poorly studied proteins. • We proposed new deep learning program to predict protein functions in silico that requires nothing more than the protein sequence information. • Due to application of sequence segmentation, the efficiency of prediction is improved. • This method makes prediction of the clinical impact of mutations or polymorphisms possible.
    Keywords FUTUSA (function teller using sequence alone) ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  2. Article ; Online: The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer.

    Kang, Ye-Lim / Kim, Jiyoung / Kwak, Su-Bin / Kim, Yi-Sook / Huh, June / Park, Jong-Wan

    Experimental & molecular medicine

    2024  Volume 56, Issue 1, Page(s) 220–234

    Abstract: Diabetes might be associated with increased cancer risk, with several studies reporting hyperglycemia as a primary oncogenic stimulant. Since glucose metabolism is linked to numerous metabolic pathways, it is difficult to specify the mechanisms ... ...

    Abstract Diabetes might be associated with increased cancer risk, with several studies reporting hyperglycemia as a primary oncogenic stimulant. Since glucose metabolism is linked to numerous metabolic pathways, it is difficult to specify the mechanisms underlying hyperglycemia-induced cancer progression. Here, we focused on the polyol pathway, which is dramatically activated under hyperglycemia and causes diabetic complications. We investigated whether polyol pathway-derived fructose facilitates hyperglycemia-induced gastric cancer metastasis. We performed bioinformatics analysis of gastric cancer datasets and immunohistochemical analyses of gastric cancer specimens, followed by transcriptomic and proteomic analyses to evaluate phenotypic changes in gastric cancer cells. Consequently, we found a clinical association between the polyol pathway and gastric cancer progression. In gastric cancer cell lines, hyperglycemia enhanced cell migration and invasion, cytoskeletal rearrangement, and epithelial-mesenchymal transition (EMT). The hyperglycemia-induced acquisition of metastatic potential was mediated by increased fructose derived from the polyol pathway, which stimulated the nuclear ketohexokinase-A (KHK-A) signaling pathway, thereby inducing EMT by repressing the CDH1 gene. In two different xenograft models of cancer metastasis, gastric cancers overexpressing AKR1B1 were found to be highly metastatic in diabetic mice, but these effects of AKR1B1 were attenuated by KHK-A knockdown. In conclusion, hyperglycemia induces fructose formation through the polyol pathway, which in turn stimulates the KHK-A signaling pathway, driving gastric cancer metastasis by inducing EMT. Thus, the polyol and KHK-A signaling pathways could be potential therapeutic targets to decrease the metastatic risk in gastric cancer patients with diabetes.
    MeSH term(s) Humans ; Animals ; Mice ; Stomach Neoplasms/genetics ; Stomach Neoplasms/metabolism ; Diabetes Mellitus, Experimental ; Proteomics ; Signal Transduction ; Hyperglycemia/complications ; Fructokinases/genetics ; Fructokinases/metabolism ; Fructose/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Cell Movement/genetics ; Cell Line, Tumor ; Aldehyde Reductase/genetics ; Aldehyde Reductase/metabolism ; Aldehyde Reductase/pharmacology ; Polymers
    Chemical Substances polyol ; Fructokinases (EC 2.7.1.-) ; Fructose (30237-26-4) ; AKR1B1 protein, human (EC 1.1.1.21) ; Aldehyde Reductase (EC 1.1.1.21) ; Polymers
    Language English
    Publishing date 2024-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1328915-9
    ISSN 2092-6413 ; 1226-3613 ; 0378-8512
    ISSN (online) 2092-6413
    ISSN 1226-3613 ; 0378-8512
    DOI 10.1038/s12276-023-01153-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Deep learning program to predict protein functions based on sequence information.

    Ko, Chang Woo / Huh, June / Park, Jong-Wan

    MethodsX

    2022  Volume 9, Page(s) 101622

    Abstract: Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We ... ...

    Abstract Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We designed a binary classification deep learning program requiring only sequence information. This program was named 'FUTUSA' (function teller using sequence alone). It applied sequence segmentation during the sequence feature extraction process, by a convolution neural network, to train the regional sequence patterns and their relationship. This segmentation process improved the predictive performance by 49% than the full-length process. Compared with a baseline method, our approach achieved higher performance in predicting oxidoreductase activity. In addition, FUTUSA also showed dramatic performance in predicting acetyltransferase and demethylase activities. Next, we tested the possibility that FUTUSA can predict the functional consequence of point mutation. After trained for monooxygenase activity, FUTUSA successfully predicted the impact of point mutations on phenylalanine hydroxylase, which is responsible for an inherited metabolic disease PKU. This deep-learning program can be used as the first-step tool for characterizing newly identified or poorly studied proteins.•We proposed new deep learning program to predict protein functions in silico that requires nothing more than the protein sequence information.•Due to application of sequence segmentation, the efficiency of prediction is improved.•This method makes prediction of the clinical impact of mutations or polymorphisms possible.
    Language English
    Publishing date 2022-01-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2022.101622
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Hypoxia-driven epigenetic regulation in cancer progression: A focus on histone methylation and its modifying enzymes.

    Kim, Iljin / Park, Jong-Wan

    Cancer letters

    2020  Volume 489, Page(s) 41–49

    Abstract: The mechanism underlying hypoxia-driven chromatin remodeling is a long-lasting question. For the last two decades, this question has been resolved in part. It is now widely agreed that hypoxia dynamically changes the methylation status of histones to ... ...

    Abstract The mechanism underlying hypoxia-driven chromatin remodeling is a long-lasting question. For the last two decades, this question has been resolved in part. It is now widely agreed that hypoxia dynamically changes the methylation status of histones to control gene expression. Hypoxia-inducible factor (HIF) plays a central role in cellular responses to hypoxia through transcriptional activation of numerous genes. At least in part, the hypoxic regulation of histone methylation is attributed to the HIF-mediated expression of histone modifying enzymes. Protein hydroxylation and histone demethylation have emerged as the oxygen sensing processes because they are catalyzed by a family of 2-oxoglutarate (2OG)-dependent dioxygenases whose activities depend upon the ambient oxygen level. Recently, it has been extensively investigated that the 2OG dioxygenases oxygen-dependently regulate histone methylation. Nowadays, the hypoxic change in the histone methylation status is regarded as an important event to drive malignant behaviors of cancer cells. In this review, we introduced and summarized the cellular processes that govern hypoxia-driven regulation of histone methylation in the context of cancer biology. We also discussed the emerging roles of histone methyltransferases and demethylases in epigenetic response to hypoxia.
    MeSH term(s) Animals ; Cell Hypoxia/genetics ; DNA Methylation/genetics ; Disease Progression ; Gene Expression Regulation, Neoplastic/genetics ; Histones/genetics ; Humans ; Neoplasms/genetics ; Neoplasms/pathology
    Chemical Substances Histones
    Language English
    Publishing date 2020-06-06
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2020.05.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: Deep learning program to predict protein functions based on sequence information

    Ko, Chang Woo / Huh, June / Park, Jong-Wan

    MethodsX. 2022, v. 9

    2022  

    Abstract: Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We ... ...

    Abstract Deep learning technologies have been adopted to predict the functions of newly identified proteins in silico. However, most current models are not suitable for poorly characterized proteins because they require diverse information on target proteins. We designed a binary classification deep learning program requiring only sequence information. This program was named ‘FUTUSA’ (function teller using sequence alone). It applied sequence segmentation during the sequence feature extraction process, by a convolution neural network, to train the regional sequence patterns and their relationship. This segmentation process improved the predictive performance by 49% than the full-length process. Compared with a baseline method, our approach achieved higher performance in predicting oxidoreductase activity. In addition, FUTUSA also showed dramatic performance in predicting acetyltransferase and demethylase activities. Next, we tested the possibility that FUTUSA can predict the functional consequence of point mutation. After trained for monooxygenase activity, FUTUSA successfully predicted the impact of point mutations on phenylalanine hydroxylase, which is responsible for an inherited metabolic disease PKU. This deep-learning program can be used as the first-step tool for characterizing newly identified or poorly studied proteins.•We proposed new deep learning program to predict protein functions in silico that requires nothing more than the protein sequence information.•Due to application of sequence segmentation, the efficiency of prediction is improved.•This method makes prediction of the clinical impact of mutations or polymorphisms possible.
    Keywords acetyltransferases ; amino acid sequences ; computer simulation ; inherited metabolic diseases ; phenylalanine 4-monooxygenase ; point mutation ; prediction
    Language English
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2830212-6
    ISSN 2215-0161
    ISSN 2215-0161
    DOI 10.1016/j.mex.2022.101622
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  6. Article ; Online: Comparison of Fatigue Performances Based on Shape Change of Rail Fastening Spring

    Xiao-Jun Fang / Yeun-Chul Park / Jong-Wan Hu / Hyoung-Bo Sim

    Applied Sciences, Vol 13, Iss 1770, p

    2023  Volume 1770

    Abstract: The fastening spring of a rail fastening system serves as an important connection in transferring the train load to the sleeper via rails on railway tracks. During initial fastening, a large tensile stress exceeding the yield stress can occur in the ... ...

    Abstract The fastening spring of a rail fastening system serves as an important connection in transferring the train load to the sleeper via rails on railway tracks. During initial fastening, a large tensile stress exceeding the yield stress can occur in the fastening spring structure, making it vulnerable to fatigue owing to stress fluctuations during train use. The damage caused by fatigue in the fastening springs have been reported for rail fastening systems on several domestic and international routes; however, research on this topic is limited. This study evaluates the fatigue performance of a fastening spring, SPS9 spring steel, developed in Korea based on shape change by performing a sensitivity analysis of various factors, including the heights at the end of the fastening spring and the spring arm, overall lateral width, and the diameter of the cross section of the fastening spring. The modified Goodman fatigue diagram was applied based on the tensile stress on initial fastening and the constant stress range due to a rail vertical displacement caused by train use through finite element analysis. The fatigue analysis showed that the lateral width and diameter factors of the fastening spring are found to be important variables for fatigue performance. Moreover, as the width and diameter increase, the fatigue performance improves significantly. The fatigue safety margin increased from 64% to 82% when the width increased from −20% to +20%, and increased from 54% to 81% with the diameter increase from 13 mm to 18 mm.
    Keywords rail fastening system ; railway track ; fastening spring ; fatigue ; finite element analysis ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
    Subject code 669
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  7. Article ; Online: Development of a rectally administrable Dnase1 to treat septic shock by targeting NETs.

    Kwak, Su-Bin / Kim, Sang-Jin / Kang, Yeon Jun / Lee, Won-Woo / Huh, June / Park, Jong-Wan

    Life sciences

    2024  Volume 342, Page(s) 122526

    Abstract: Aims: Neutrophil extracellular trap (NET), which is formed by DNA threads, induces septic shock by aggravating systemic inflammation. An intravenous administration of deoxyribonuclease is regarded as a compelling modality for treating septic shock. ... ...

    Abstract Aims: Neutrophil extracellular trap (NET), which is formed by DNA threads, induces septic shock by aggravating systemic inflammation. An intravenous administration of deoxyribonuclease is regarded as a compelling modality for treating septic shock. However, alternative routes should be chosen when cutaneous veins are all collapsed due to hypotension. In this study, we genetically engineered this enzyme to develop a rectal suppository formulation to treat septic shock.
    Main methods: Dnase1 was mutated at two amino acid residues to increase its stability in the blood and fused with a cell-penetrating peptide CR8 to increase its absorption through the rectal mucosa, which is designated AR-CR8. The life-saving effect of AR-CR8 was evaluated in a LPS-induced shock mouse model.
    Key findings: AR-CR8 was shown to remove NETs effectively in human neutrophils. When AR-CR8 was administered to the mouse rectum, the deoxyribonuclease activity in the mouse serum was significantly increased. In the LPS-induced shock model, 90 % of the control mice died over 72 h after LPS injection. In contrast, the rectal administration of AR-CR8 showed a mortality rate of 30 % by 72 h after LPS injection. The Log-rank test revealed that the survival rate is significantly higher in the AR-CR8 group. The NET markers in the mouse serum were enhanced by LPS, and significantly downregulated in the AR-CR8 group. These results suggest that AR-CR8 ameliorates LPS-induced shock by degrading NETs.
    Significance: The engineered DNASE1 could be developed as a rectal suppository formulation to treat septic shock urgently at out-of-hospital places where no syringe is available.
    MeSH term(s) Animals ; Humans ; Mice ; Extracellular Traps ; Shock, Septic/drug therapy ; Shock, Septic/chemically induced ; Shock, Septic/metabolism ; Lipopolysaccharides/adverse effects ; Neutrophils/metabolism ; Deoxyribonucleases/metabolism
    Chemical Substances Lipopolysaccharides ; Deoxyribonucleases (EC 3.1.-)
    Language English
    Publishing date 2024-02-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2024.122526
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: SUV39H1-driven NFATc1 methylation is essential for the c-Cbl-mediated degradation of NFATc1 in an osteoclast lineage.

    Jeong, Do-Won / Kim, Hye-Jin / Park, Jong-Wan / Lee, Seulbee / Jung, Hyeryeon / Yi, Eugene C / Kim, Nacksung / Chun, Yang-Sook

    Genes & diseases

    2023  Volume 11, Issue 4, Page(s) 101034

    Language English
    Publishing date 2023-07-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2821806-1
    ISSN 2352-3042 ; 2352-3042
    ISSN (online) 2352-3042
    ISSN 2352-3042
    DOI 10.1016/j.gendis.2023.06.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article: SPATA20 deficiency enhances the metastatic and angiogenic potential of cancer cells by promoting HIF-1α synthesis.

    Choi, Sanga / Yoo, Seongkyeong / Jeon, Miyeon / Park, Soohyun / Choi, Yunsup / An, Jiyeon / Jeon, Sungmi / Lee, Mingyu / Yun, Jang-Hyuk / Park, Jong-Wan / Kim, Iljin

    American journal of cancer research

    2024  Volume 14, Issue 2, Page(s) 727–743

    Abstract: Hypoxia-inducible factors (HIFs) regulate cellular oxygen balance and play a central role in cancer metastasis and angiogenesis. Despite extensive research on HIFs, successful therapeutic strategies remain limited due to the intricate nature of their ... ...

    Abstract Hypoxia-inducible factors (HIFs) regulate cellular oxygen balance and play a central role in cancer metastasis and angiogenesis. Despite extensive research on HIFs, successful therapeutic strategies remain limited due to the intricate nature of their regulation. In this study, we identified SPATA20, a relatively understudied protein with a thioredoxin-like domain, as an upstream regulator of HIF-1α. Depleting SPATA20 induced HIF-1α expression, suggesting a tumor-suppressive role for SPATA20 in cancer cells. SPATA20 depletion increased HIF-1α protein levels and transcriptional activity without affecting its degradation. It appears that SPATA20 inhibits the
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Loop and Bridge Conformations of ABA Triblock Comb Copolymers: A Conformational Assessment for Molecular Composites.

    Park, Jihoon / Jung, Je-Yeon / Shin, Hyun-Woo / Park, Jong-Wan / Bang, Joona / Huh, June

    Polymers

    2022  Volume 14, Issue 11

    Abstract: We computationally investigate the conformational behavior, "bridging" chain, between different the phase-separated domains vs "looping" chain on the same domain, for two chain architectures of ABA triblock copolymers, one with a linear architecture (L- ... ...

    Abstract We computationally investigate the conformational behavior, "bridging" chain, between different the phase-separated domains vs "looping" chain on the same domain, for two chain architectures of ABA triblock copolymers, one with a linear architecture (L-TBC) and the other with comb architecture (C-TBC) at various segregation regimes using dissipative particle dynamics (DPD) simulations. The power-law relation between the bridge fraction (Φ) and the interaction parameter (χ) for C-TBC is found to be Φ∼χ-1.6 in the vicinity of the order-disorder transition (χODT), indicating a drastic conversion from the bridge to the loop conformation. When χ further increases, the bridge-loop conversions slow down to have the power law, Φ∼χ-0.18, approaching the theoretical power law Φ∼χ-1/9 predicted in the strong segregation limit. The conformational assessment conducted in the present study can provide a strategy of designing optimal material and processing conditions for triblock copolymer either with linear or comb architecture to be used for thermoplastic elastomer or molecular nanocomposites.
    Language English
    Publishing date 2022-06-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527146-5
    ISSN 2073-4360 ; 2073-4360
    ISSN (online) 2073-4360
    ISSN 2073-4360
    DOI 10.3390/polym14112301
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top