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A novel biomechanical model of the proximal mouse forelimb predicts muscle activity in optimal control simulations of reaching movements

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Journal of Neurophysiology 2025年第4期133卷 1266-1278页

作者： Gilmer, Jesse I. Coltman, Susan K. Cuenu, Geraldine Hutchinson, John R. Huber, Daniel Person, Abigail L. Borno, Mazen Al Department of Computer Science and Engineering Computational Bioscience Program University of Colorado Denver j Anschutz Medical Campus Denver CO United States Department of Basic Neuroscience University of Geneva Geneva Switzerland Department of Physiology and Biophysics University of Colorado Denver j Anschutz Medical Campus Denver CO United States Department of Comparative Biomedical Sciences Royal Veterinary College London United Kingdom Department of Kinesiology The Pennsylvania State University University Park PA United States

Mice are key model organisms in neuroscience and motor systems physiology. Fine motor control tasks performed by mice have become widely used in assaying neural and biophysical motor system mechanisms. Although fine motor tasks provide useful insights into behaviors that require complex multi-joint motor control, there is no previously developed physiological biomechanical model of the adult mouse forelimb available for estimating kinematics, muscle activity, or kinetics during behaviors. Here, we developed a musculoskeletal model based on high-resolution imaging of the mouse forelimb that includes muscles spanning the neck, trunk, shoulder, and limbs. Physics-based optimal control simulations of the forelimb model were used to estimate in vivo muscle activity present when constrained to the tracked kinematics during reaching movements. The activity of a subset of muscles was recorded and used to assess the accuracy of the muscle patterning in simulation. We found that the synthesized muscle patterning in the forelimb model had a strong resemblance to empirical muscle patterning, suggesting that our model has utility in providing a realistic set of estimated muscle excitations over time when given a kinematic template. The strength of the similarity between empirical muscle activity and optimal control predictions increases as mice performance improves throughout learning of the reaching task. Our computational tools are available as open-source in the OpenSim physics and modeling platform. Our model can enhance research into limb control across broad research topics and can inform analyses of motor learning, muscle synergies, neural patterning, and behavioral research that would otherwise be inaccessible. NEW & NOTEWORTHY Investigations into motor planning and execution lack an accurate and complete model of the forelimb, which could bolster or expand on findings. We sought to construct such a model using high-detail scans of murine anatomy and prior research into

关键词： biophysical models motor control muscle patterning optimal control reaching behaviors

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EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma

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American Journal of Pathology 2025年第5期195卷 995-1012页

作者： Chanpanitkitchote, Pichaya Nuanpirom, Jiratchaya Pongsapich, Warut Asavapanumas, Nithi Mendler, Simone Wiesmann, Nadine Brieger, Juergen Jinawath, Natini Program in Molecular Medicine Faculty of Science Mahidol University Bangkok Thailand Department of Biochemistry Faculty of Science Mahidol University Bangkok Thailand Integrative Computational BioScience Center (ICBS) Mahidol University Nakhon Pathom Thailand Department of Otorhinolaryngology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand Chakri Naruebodindra Medical Institute Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand Department of Otorhinolaryngology University Medical Center Mainz Mainz Germany Department of Oral and Maxillofacial Surgery University Medical Center Mainz Mainz Germany Program in Translational Medicine Faculty of Medicine Ramathibodi Hospital Mahidol University Bangkok Thailand

Extracellular matrix (ECM) proteins play an important role in the pathological processes of tumor development and progression. Elastic microfibril interface located protein-1 (EMILIN-1), an ECM glycoprotein, is linked to cell adhesion and migration. It was identified from head and neck squamous cell carcinoma (HNSCC) tissues that down-regulated EMILIN-1. It is associated with an increased risk of secondary primary malignancy development in HNSCC and hypothesized to function as a tumor suppressor in HNSCC. This study showed that EMILIN-1 expression in HNSCC tissues was specific to the stromal area, and secreted-EMILIN-1 level was higher in fibroblasts isolated from HNSCC tissues than in HNSCC cells. EMILIN-1 overexpression decreased cell proliferation, migration, and invasion in FaDu and CAL27 cells. Knockdown of EMILIN-1 in HNSCC cancer-associated fibroblasts induced cell proliferation and migration. The conditioned medium from EMILIN-1 knockdown cancer-associated fibroblasts increased HNSCC cell proliferation, and the co-culture system enhanced cancer cell migration and invasion. RNA-sequencing analysis revealed that the cell cycle and aurora kinase signaling were the most significant enrichment pathways, confirmed at the protein level. Furthermore, in an in ovo chick chorioallantoic membrane model, overexpression of EMILIN-1 in FaDu cells reduced tumor size and Ki-67–positivity and increased cleaved caspase-3–positive cells. These findings suggest that EMILIN-1 suppresses HNSCC growth partly through the down-regulation of cell cycle and aurora kinase signaling pathways. © 2025 American Society for Investigative Pathology

关键词： Aurora kinase CAM assay Cancer associated fibroblast (CAF) EMILIN1 Extracellular matrix (ECM) HNSCC

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Molecular architecture of mammalian pyruvate dehydrogenase complex

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Protein & Cell 2025年第1期16卷 72-78页

作者： Maofei Chen Yutong Song Sensen Zhang Yitang Zhang Xudong Chen Minghui Zhang Meng Han Xin Gao Sai Li Maojun Yang Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological StructureSchool of Life SciencesTsinghua UniversityBeijing 100084China Ministry of Education Key Laboratory of Protein Science Tsinghua UniversityBeijing 100084China State Key Laboratory of Membrane Biology Tsinghua UniversityBeijing 100084China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesShenzhen University Health Science CenterShenzhen 518060China Protein Research Technology Center Protein Chemistry and Omics PlatformSchool of Life SciencesTsinghua UniversityBeijing 100084China Computer Science Program ComputerElectrical and Mathematical Sciences and Engineering DivisionKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Kingdom of Saudi Arabia Computational Bioscience Research Center King Abdullah University of Science and TechnologyThuwal 23955-6900Kingdom of Saudi Arabia Cryo-EM Facility Center Southern University of Science and TechnologyShenzhen 518055China Beijing Life Science Academy Beijing 102209China

Dear Editor,Pyruvate dehydrogenase complex(PDHc) is a large multienzyme assembly(Mr = 4–10 million Daltons) consisting of three essential components: pyruvate dehydrogenase(E1p), dihydrolipoyl transacetylase(E2p), and dihydrolipoyl dehydrogenase(E3). These three enzymes perform distinct functions sequentially to catalyze the oxidative decarboxylation of pyruvate with formation of nicotinamide adenine dinucleotide(NADH) and acetyl-coenzyme A(Patel and Roche, 1990).

关键词： sequentially oxidative Dalton

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Ontology translation: A case study on translating the gene ontology from English to German

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19th International Conference on Applications of Natural Language to Information Systems, NLDB 2014

作者： Hailu, Negacy D. Cohen, K. Bretonnel Hunter, Lawrence E. Computational Bioscience Program University of Colorado School of Medicine United States

ISBN: (纸本)9783319079820

For many researchers, the purpose of ontologies is sharing data. This sharing is facilitated when ontologies are available in multiple languages, but inhibited when an ontology is only available in a single language. Ontologies should be accessible to people in multiple languages, since multilingualism is inevitable in any scientific work. Due to resource scarcity, most ontologies of the biomedical domain are available only in English at present. We present techniques to translate Gene Ontology terms from English to German using DBPedia, the Google Translate API for isolated terms, and the Google Translate API for terms in sentential context. Average fluency scores for the three methods were 4.0, 4.4, and 4.5, respectively. Average adequacy scores were 4.0, 4.9, and 4.9. © Springer International Publishing Switzerland 2014.

关键词： Gene Ontology

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Temporal Expression Recognition for Cell Cycle Phase Concepts in Biomedical Literature

Temporal Expression Recognition for Cell Cycle Phase Concept...

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ACL 2014 Workshop on Biomedical Natural Language Processing, BioNLP 2014

作者： Hailu, Negacy D. Panteleyeva, Natalya Bretonnel Cohen, K. Computational Bioscience Program University of Colorado Denver School of Medicine United States

ISBN: (纸本)9781941643181

In this paper, we present a system for recognizing temporal expressions related to cell cycle phase (CCP) concepts in biomedical literature. We identified 11 classes of cell cycle related temporal expressions, for which we made extensions to TIMEX3, arranging them in an ontology derived from the Gene Ontology. We annotated 310 abstracts from PubMed. Annotation guidelines were developed, consistent with existing time-related annotation guidelines for TimeML. Two annotators participated in the annotation. We achieved an inter-annotator agreement of 0.79 for an exact span match and 0.82 for relaxed constraints. Our approach is a hybrid of machine learning to recognize temporal expressions and a rule-based approach to map them to the ontology. We trained a named entity recognizer using Conditional Random Fields (CRF) models. An off-the-shelf implementation of the linear chain CRF model was used. We obtained an F-score of 0.77 for temporal expression recognition. We achieved 0.79 macro-averagee F-score and 0.78 micro-averaged F-score for mapping to the ontology. ©2014 Association for computational Linguistics

关键词： Gene Ontology

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computational challenges of mass phenotyping

Computational challenges of mass phenotyping

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18th Pacific Symposium on Biocomputing, PSB 2013

作者： Hunter, Lawrence Computational Bioscience Program University of Colorado School of Medicine AuroraCO80045 United States

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Semantically integrating biomedical databases to support inference 28

Semantically integrating biomedical databases to support inf...

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28th AAAI Conference on Artificial Intelligence, AAAI 2014

作者： Livingston, Kevin M. Bada, Michael Baumgartner, William A. Hunter, Lawrence E. Computational Bioscience Program University of Colorado Anschutz Medical Campus AuroraCO United States

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The CISP annotation schema uncovers hypotheses and explanations in full-text scientific journal articles 49

The CISP annotation schema uncovers hypotheses and explanati...

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2011 Workshop on Biomedical Natural Language Processing, BioNLP 2011 at the 49th Annual Meeting of the Association for computational Linguistics: Human Language Technologies, ACL-HLT 2011

作者： White, Elizabeth Cohen, K. Bretonnel Hunter, Lawrence Department of Pharmacology Computational Bioscience Program University of Colorado School of Medicine AuroraCO United States

ISBN: (纸本)9781932432916

Increasingly, as full-text scientific papers are becoming available, scientific queries have shifted from looking for facts to looking for arguments. Researchers want to know when their colleagues are proposing theories, outlining evidentiary relations, or explaining discrepancies. We show here that sentence-level annotation with the CISP schema adapts well to a corpus of biomedical articles, and we present preliminary results arguing that the CISP schema is uniquely suited to recovering common types of scientific arguments about hypotheses, explanations, and evidence. © 2011 Association for computational Linguistics

关键词： Linguistics

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Measuring closure properties of patent sublanguages

Measuring closure properties of patent sublanguages

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9th International Conference on Recent Advances in Natural Language Processing, RANLP 2013

作者： Temnikova, Irina P. Hailu, Negacy D. Angelova, Galia Cohen, K. Bretonnel Institute of ICT Bulgarian Academy of Sciences Bulgaria Computational Bioscience Program U. Colorado School of Medicine United States

Patent search is an important information retrieval problem in scientific and business research. Semantic search would be a large improvement to current technologies, but requires some insight into the language of patents. In this article we test the fit of the language of patents to the sublanguage model, focussing on closure properties. The research presented here is relevant to the topic of sublanguage identification for different domains, and to the study of the language of patents. We investigate the hypothesis that fit to the sublanguage model increases as one moves down the International Patent Classification hierarchy. The analysis employs a general English corpus and patent documents from the MAREC corpus. It is shown that patents generally fit the sublanguage model, with some variability between categories in the extent of the fit.

关键词： Semantics

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Closure properties of Bulgarian clinical text

Closure properties of Bulgarian clinical text

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9th International Conference on Recent Advances in Natural Language Processing, RANLP 2013

作者： Temnikova, Irina P. Nikolova, Ivelina Baumgartner, William A. Angelova, Galia Cohen, K. Bretonnel Institute of ICT Bulgarian Acad. of Sciences Bulgaria Computational Bioscience Program U. Colorado School of Medicine United States

Sublanguages are specialized genres of language associated with specific domains and document types. When sublanguages can be recognized and adequately characterized, they are useful for a variety of types of natural language processing applications. Although there are sublanguage studies related to languages other than English, all previous work on sublanguage recognition has focused on sublanguages related to general English. This paper tests whether a sublanguage detecting technique developed for English can be applied to another language. Bulgarian clinical documents are an excellent test case, because of a number of unique linguistic properties that affect their lexical and morphological characteristics. Bulgarian clinical documents were studied with respect to their closure properties and were found to fit the sublanguage model and exhibit characteristics like those noted for sublanguages related to English. It was also confirmed that the clinical sublanguage phenomenon is not a coincidental phenomenon of English, but applies to other languages as well. Implications of this fact for natural language processing are proposed.

关键词： Natural language processing systems

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