检索结果-内蒙古大学图书馆

International Conference on Big Data and Smart Computing (BIGCOMP)

作者： Doyeong Hwang Minji Jeon Jaewoo Kang Department of Computer Science and Engineering Korea University Seoul Republic of Korea Interdisciplinary Graduate Program in Bioinformatics Korea University Seoul Republic of Korea

ISBN: (数字)9781728160344

ISBN: (纸本)9781728160351

Drug-Induced Liver Injury (DILI) is a major cause of failed drug candidates in clinical trials and withdrawal of approved drugs from the market. Therefore, machine learning-based DILI prediction can be key in increasing the success rate of drug discovery because drug candidates that are predicted to potentially induce liver injury can be rejected before clinical trials. However, existing DILI prediction models mainly focus on the chemical structures of drugs. Since we cannot determine whether a drug will cause liver injury based solely on its structure, DILI prediction based on the transcriptional effect of a drug on a cell is necessary. In this paper, we propose GLIT which is a model that uses transcriptional response data and chemical structures and can be used for drug-induced liver injury prediction. GLIT learns the embedding vectors of drug structures and drug-induced gene expression profiles using graph attention networks in a biological knowledge graph for predicting DILI. GLIT outperformed a baseline model that uses only drug structure information by 7% and 19.2% in terms of correct classification rate (CCR) and Matthews correlation coefficient (MCC), respectively. In addition, we conducted a literature survey to confirm whether the class labels of drugs, in the unknown DILI class, predicted by GLIT are correct.

关键词： Drugs Gene expression Neural networks Injuries Liver Predictive models Biological system modeling

来源：评论

学校读者我要写书评

暂无评论

Core packing of well-defined x-ray and NMR structures is the same

arXiv

引用

arXiv 2022年

作者： Grigas, Alex T. Liu, Zhuoyi Regan, Lynne O’Hern, Corey S. Graduate Program in Computational Biology and Bioinformatics Yale University New HavenCT06520 United States Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06520 United States Department of Mechanical Engineering and Materials Science Yale University New HavenCT06520 United States Institute of Quantitative Biology Biochemistry and Biotechnology Centre for Synthetic and Systems Biology School of Biological Sciences University of Edinburgh United Kingdom Department of Physics Yale University New HavenCT06520 United States Department of Applied Physics Yale University New HavenCT06520 United States

Numerous studies have investigated the differences and similarities between protein structures determined by solution NMR spectroscopy and those determined by x-ray crystallography. A fundamental question is whether any observed differences are due to differing methodologies, or to differences in the behavior of proteins in solution versus in the crystalline state. Here, we compare the properties of the hydrophobic cores of high-resolution protein crystal structures and those in NMR structures, determined using increasing numbers and types of restraints. Prior studies have reported that many NMR structures have denser cores compared to those of high-resolution x-ray crystal structures. Our current work investigates this result in more detail, and finds that these NMR structures tend to violate basic features of protein stereochemistry, such as small non-bonded atomic overlaps and few Ramachandran and side chain dihedral angle outliers. We find that NMR structures solved with more restraints, and which do not significantly violate stereochemistry, have hydrophobic cores that have a similar size and packing fraction as their counterparts determined by x-ray crystallography at high-resolution. These results lead us to conclude that, at least regarding the core packing properties, high-quality structures determined by NMR and x-ray crystallography are the same, and the differences reported earlier are most likely a consequence of methodology, rather than fundamental differences between the protein in the two different environments. Significance: Dense packing of hydrophobic residues is key to protein structure and stability. Previously, it has been noted that structures solved by NMR spectroscopy have denser cores than x-ray crystal structures. Here, we calculate the core size and packing fraction of NMR structures with experimental restraints in the PDB. Their cores are typically smaller, but denser. However, NMR structures with accurate stereochemistry possess core pa

关键词： X ray crystallography

来源：评论

学校读者我要写书评

暂无评论

How Retroactivity Affects the Behavior of Incoherent Feed-Forward Loops

arXiv

引用

arXiv 2020年

作者： Wang, Junmin Belta, Calin Isaacson, Samuel A. Bioinformatics Graduate Program Boston University BostonMA United States Department of Mathematics and Statistics Boston University BostonMA United States

An incoherent feed-forward loop (IFFL) is a network motif known for its ability to accelerate responses and generate pulses. Though functions of IFFLs are well studied, most previous computational analysis of IFFLs used ordinary differential equation (ODE) models where retroactivity, the effect downstream binding sites exert on the dynamics of an upstream transcription factor (TF), was not considered. It remains an open question to understand the behavior of IFFLs in contexts with high levels of retroactivity, e.g., in cells transformed/transfected with high-copy plasmids, or in eukaryotic cells where a TF binds to numerous high-affinity binding sites in addition to one or more functional target sites. Here we study the behavior of IFFLs by simulating and comparing ODE models with different levels of retroactivity. We find that increasing retroactivity in an IFFL can increase, decrease, or keep the network’s response time and pulse amplitude constant. This suggests that increasing retroactivity, traditionally considered as an impediment to designing robust synthetic systems, could be exploited to improve the performance of IFFLs. We compare the behaviors of IFFLs to negative autoregulatory loops, another sign-sensitive response-accelerating network motif, and find that increasing retroactivity in a negative autoregulated circuit can only slow the response. The inability of a negative autoregulatory loop to flexibly handle retroactivity may have contributed to its lower abundance in eukaryotic relative to bacterial regulatory networks, a sharp contrast to the significant abundance of IFFLs in both cell types. Copyright © 2020, The Authors. All rights reserved.

关键词： Transcription

来源：评论

学校读者我要写书评

暂无评论

Functional neuroplasticity of facilitation and interference effects on inhibitory control following 3-month physical exercise in aging

引用

Scientific Reports 2024年第1期14卷 1-13页

作者： Wu, Hong-Yi Huang, Chih-Mao Hsu, Ai-Ling Chen, Chiao-Nan Wu, Changwei W. Chen, Jyh-Horng Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Bachelor Program in Artificial Intelligence Chang Gung University Taoyuan Taiwan Department of Psychiatry Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan Department of Physical Therapy and Assistive Technology National Yang Ming Chiao Tung University Taipei Taiwan Graduate Institute of Mind Brain and Consciousness Taipei Medical University New Taipei Taiwan Research Center of Sleep Medicine Taipei Medical University Hospital Taipei Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan

Preservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention;however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilita

关键词：

来源：评论

学校读者我要写书评

暂无评论

Bile acid synthesis impedes tumor-specific T cell responses during liver cancer

引用

Science (New York, N.Y.) 2025年第6730期387卷 192-201页

作者： Varanasi, Siva Karthik Chen, Dan Liu, Yingluo Johnson, Melissa A. Miller, Cayla M. Ganguly, Souradipta Lande, Kathryn LaPorta, Michael A. Hoffmann, Filipe Araujo Mann, Thomas H. Teneche, Marcos G. Casillas, Eduardo Mangalhara, Kailash C. Mathew, Varsha Sun, Ming Jensen, Isaac J. Farsakoglu, Yagmur Chen, Timothy Parisi, Bianca Deota, Shaunak Havas, Aaron Lee, Jin Chung, H Kay Schietinger, Andrea Panda, Satchidananda Williams, April E. Farber, Donna L. Dhar, Debanjan Adams, Peter D. Feng, Gen-Sheng Shadel, Gerald S. Sundrud, Mark S. Kaech, Susan M. NOMIS Center for Immunobiology and Microbial Pathogenesis Salk Institute for Biological Studies La Jolla CA United States Department of Pathology School of Medicine University of California San Diego La Jolla CA United States Sanford Burnham Prebys Medical Discovery Institute La Jolla CA United States Department of Medicine School of Medicine University of California San Diego CA United States Razavi Newman Integrative Genomics and Bioinformatics Core Facility Salk Institute for Biological Studies La Jolla CA United States Department of Microbiology and Immunology Columbia University Irving Medical Center New York NY USA Department of Surgery Columbia University Irving Medical Center New York NY USA Regulatory Biology Laboratory Salk Institute for Biological Studies La Jolla CA United States Immunology Program Memorial Sloan Kettering Cancer Center New York NY USA Immunology and Microbial Pathogenesis Program Weill Cornell Graduate School of Medical Sciences New York NY USA Parker Institute for Cancer Immunotherapy New York NY USA Department of Microbiology and Immunology Geisel School of Medicine at Dartmouth Hanover NH USA Department of Medicine Geisel School of Medicine at Dartmouth Hanover NH USA Center for Digestive Health Dartmouth Health NH United States Dartmouth Cancer Center Dartmouth Health NH United States

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. Furthermore, different BAs regulated CD8+ T cells differently;primary BAs induced oxidative stress, whereas the secondary BA lithocholic acid inhibited T cell function through endoplasmic reticulum stress, which was countered by ursodeoxycholic acid. We demonstrate that modifying BA synthesis or dietary intake of ursodeoxycholic acid could improve tumor immunotherapy in liver cancer model systems.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Phosphoproteomic analysis reveals distinctive responses in Mangrovibacter phragmatis under high-salinity condition

引用

Biochemical and biophysical research communications 2024年 736卷 150514页

作者： Hong Soon Chin Narendrakumar Ravi Varadharajulu Zhi-Han Lin Chuan-Chih Hsu Steve S-F Yu Institute of Chemistry Academia Sinica Taipei Taiwan Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan Institute of Bioinformatics and Structural Biology National Tsing Hua University Hsinchu Taiwan. Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan Department of Chemistry National Tsing Hua University Hsinchu Taiwan. Institute of Biochemical Sciences National Taiwan University Taipei Taiwan. Institute of Plant and Microbial Biology Academia Sinica Taipei Taiwan. Molecular Science and Technology Program Taiwan International Graduate Program Academia Sinica Taipei Taiwan. Electronic address: sfyu@gate.sinica.edu.tw.

We conducted a thorough genome-wide investigation of protein phosphorylation in the halotolerant bacterium Mangrovibacter phragmitis (MPH) ASIOC01, using the Fe-IMAC enrichment method combined with tandem mass spectrometry under low- and high-salinity conditions. The phosphoproteome comprises 86 unique phosphorylated proteins, crucially involving pathways such as glycolysis/gluconeogenesis, the citrate cycle, chaperones, ribosomal proteins, and cell division. This study represents the first and most extensive investigation to-date comparing the bacterial phosphoproteome under different osmotic conditions using a gel-free approach. We identified 45 unique phosphoproteins in MPH cultured in media containing 1 % NaCl, and 33 exclusive phosphoproteins in MPH cultured in media containing 5 % NaCl. Eight phosphoproteins were detected in both growth conditions. Analysis of high-confidence phosphosites reveals that phosphorylation predominantly occurs on serine residues (52.3 %), followed by threonine (35.1 %) and tyrosine (12.6 %) residues. Interestingly, 34 % of the phosphopeptides display multiple phosphosites. Currently, prokaryotic phosphorylation site prediction platforms like MPSite and NetPhosBac 1.0 demonstrate an average prediction accuracy of only 21 % when applied to our dataset. Fourteen phosphoproteins did not yield matches when compared against dbPSP 2.0 (database of Phosphorylation Sites in Prokaryotes), indicating that these proteins may be novel phosphoproteins. These unique proteins undergoing phosphorylation under high salinity growth conditions potentially enhance their adaptive capabilities to environmental challenges.

关键词： Halotolerance LC-MS/MS Mangrovibacter phragmitis Osmotic-stress Phosphoproteomes Ser/thr/tyr phosphorylation

来源：评论

学校读者我要写书评

暂无评论

Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer's disease

引用

Cell 2025年

作者： Chen, Junchen Hadi, Fatemeh Wen, Xingzhao Zhao, Wenxin Xu, Ming Xue, Shuanghong Lin, Pei Calandrelli, Riccardo Richard, John Lalith Charles Song, Zhixuan Li, Jessica Amani, Alborz Liu, Yang Chen, Xu Zhong, Sheng Shu Chien-Gene Lay Department of Bioengineering University of California San Diego La Jolla San Diego CA United States Institute of Engineering in Medicine University of California San Diego La Jolla San Diego CA United States Program in Bioinformatics and Systems Biology University of California San Diego La Jolla San Diego CA United States School of Biological Sciences University of California San Diego La Jolla San Diego CA United States Department of Neurosciences University of California San Diego La Jolla San Diego CA United States Neuroscience Graduate Program University of California San Diego La Jolla San Diego CA United States

Virtually all individuals aged 65 or older develop at least early pathology of Alzheimer's disease (AD), yet most lack disease-causing mutations in APP, PSEN, or MAPT, and many do not carry the APOE4 risk allele. This raises questions about AD development in the general population. Although transcriptional dysregulation has not traditionally been a hallmark of AD, recent studies reveal significant epigenomic changes in late-onset AD (LOAD) patients. We show that altered expression of the LOAD biomarker phosphoglycerate dehydrogenase (PHGDH) modulates AD pathology in mice and human brain organoids independent of its enzymatic activity. PHGDH has an uncharacterized role in transcriptional regulation, promoting the transcription of inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKa) and high-mobility group box 1 (HMGB1) in astrocytes, which suppress autophagy and accelerate amyloid pathology. A blood-brain-barrier-permeable small-molecule inhibitor targeting PHGDH's transcriptional function reduces amyloid pathology and improves AD-related behavioral deficits. These findings highlight transcriptional regulation in LOAD and suggest therapeutic strategies beyond targeting familial mutations. © 2025 The Author(s)

关键词： Alzheimer's disease amyloid pathology astrocyte biomarker LOAD PHGDH small molecule therapeutic candidate transcriptional regulation

来源：评论

学校读者我要写书评

暂无评论

Application for sugarcane plantation: Manpower and transportation planning

引用

AIP Conference Proceedings 2023年第1期2594卷

作者： H. G. Mawandha D. Sudigyo T. Suparyanto B. Pardamean Department of Agrotechnology Institute of Agriculture STIPER Yogyakarta Indonesia 55281 Bioinformatics & Data Science Research Center Bina Nusantara University Jakarta Indonesia 11480 Computer Science Department BINUS Graduate Program - Master of Computer Science Program Bina Nusantara University Jakarta Indonesia 11480

Sugarcane plantations in Indonesia are still managed in a labor-intensive manner, especially plantation-owned by farmers. Labor intensive means that every stage of work in sugarcane plantation management still uses manpower. One of the jobs in sugarcane plantations that requires a lot of labor is sugar cane harvesting. Trend changing in the workforce gender would affect the quantity and quality of jobs, which is determined by the workforce's capacity and the workload of the work performed. The result of this research was a sugarcane agricultural calculator that made it simple for farmers to measure manpower and transportation requirements in estimating harvest costs. Manpower and transportation of harvested sugarcane commodities were estimated through the workload approach, namely, crop production and manpower's ability to carry a load. These two components helped sugarcane farmers to determine manpower and transportation during the harvest. The final yield produced by the projected harvest labor cost would be known immediately.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Evaluation of GPT and BERT-based models on identifying protein-protein interactions in biomedical text

arXiv

引用

arXiv 2023年

作者： Rehana, Hasin Çam, Nur Bengisu Basmaci, Mert Zheng, Jie Jemiyo, Christianah He, Yongqun Özgür, Arzucan Hur, Junguk Computer Science Graduate Program University of North Dakota Grand ForksND58202 United States Department of Computer Engineering Bogazici University Istanbul34342 Turkey Unit for Laboratory Animal Medicine Department of Microbiology and Immunology University of Michigan Ann ArborMI48109 United States Department of Biomedical Sciences University of North Dakota School of Medicine and Health Sciences Grand ForksND58202 United States Center for Computational Medicine and Bioinformatics University of Michigan Ann ArborMI48109 United States

Detecting protein-protein interactions (PPIs) is crucial for understanding genetic mechanisms, disease pathogenesis, and drug design. However, with the fast-paced growth of biomedical literature, there is a growing need for automated and accurate extraction of PPIs to facilitate scientific knowledge discovery. Pre-trained language models, such as generative pre-trained transformers (GPT) and bidirectional encoder representations from transformers (BERT), have shown promising results in natural language processing (NLP) tasks. We evaluated the performance of PPI identification of multiple GPT and BERT models using three manually curated gold-standard corpora: Learning Language in Logic (LLL) with 164 PPIs in 77 sentences, Human Protein Reference Database with 163 PPIs in 145 sentences, and Interaction Extraction Performance Assessment with 335 PPIs in 486 sentences. BERT-based models achieved the best overall performance, with BioBERT achieving the highest recall (91.95%) and F1-score (86.84%) and PubMedBERT achieving the highest precision (85.25%). Interestingly, despite not being explicitly trained for biomedical texts, GPT-4 achieved commendable performance, comparable to the top-performing BERT models. It achieved a precision of 88.37%, a recall of 85.14%, and an F1-score of 86.49% on the LLL dataset. These results suggest that GPT models can effectively detect PPIs from text data, offering promising avenues for application in biomedical literature mining. Further research could explore how these models might be fine-tuned for even more specialized tasks within the biomedical domain. © 2023, CC BY.

关键词： Extraction

来源：评论

学校读者我要写书评

暂无评论

Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus(vol 7, 15, 2024)

COMMUNICATIONS BIOLOGY

引用

COMMUNICATIONS BIOLOGY 2024年第1期7卷 15页

作者： Salem, Gielenny M. Galula, Jedhan Ucat Wu, Shang-Rung Liu, Jyung-Hurng Chen, Yen-Hsu Wang, Wen-Hung Wang, Sheng-Fan Song, Cheng-Sheng Chen, Fan-Chi Abarientos, Adrian B. Chen, Guan-Wen Wang, Cheng-, I Chao, Day-Yu Graduate Institute of Microbiology and Public Health College of Veterinary Medicine National Chung Hsing University Taichung City 402 Taiwan. Institute of Oral Medicine School of Dentistry College of Medicine National Cheng Kung University Tainan City 701 Taiwan. Graduate Institute of Genomics and Bioinformatics College of Life Sciences National Chung Hsing University Taichung City 40227 Taiwan. School of Medicine College of Medicine National Sun Yat-Sen University Kaohsiung City 80424 Taiwan. Center for Tropical Medicine and Infectious Disease Research Kaohsiung Medical University Kaohsiung City 80708 Taiwan. Doctoral Program in Microbial Genomics National Chung Hsing University and Academia Sinica Taichung City 402 Taiwan. Singapore Immunology Network Agency for Science Technology and Research (A*STAR) 8A Biomedical Grove Immunos Singapore 138648 Singapore. Graduate Institute of Microbiology and Public Health College of Veterinary Medicine National Chung Hsing University Taichung City 402 Taiwan. dychao@nchu.edu.tw.

Exposure to multiple mosquito-borne flaviviruses within a lifetime is not uncommon; however, how sequential exposures to different flaviviruses shape the cross-reactive humoral response against an antigen from a different serocomplex has yet to be explored. Here, we report that dengue-infected individuals initially primed with the Japanese encephalitis virus (JEV) showed broad, highly neutralizing potencies against Zika virus (ZIKV). We also identified a rare class of ZIKV-cross-reactive human monoclonal antibodies with increased somatic hypermutation and broad neutralization against multiple flaviviruses. One huMAb, K8b, binds quaternary epitopes with heavy and light chains separately interacting with overlapping envelope protein dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. JEV virus-like particle immunization in mice further confirmed that such cross-reactive antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous dengue virus (DENV) serotype 2 virus-like particle stimulation. Our findings highlight the role of prior immunity in JEV and DENV in shaping the breadth of humoral response and provide insights for future vaccination strategies in flavivirus-endemic countries.

关键词：

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：