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A disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization

Molecular Cell 2025年

作者： Tim M. Gemeinhardt Roshan M. Regy Tien M. Phan Nanu Pal Jyoti Sharma Olga Senkovich Andrea J. Mendiola Heather J. Ledterman Amy Henrickson Daniel Lopes Utkarsh Kapoor Ashish Bihani Djamouna Sihou Young C. Kim David Jeruzalmi Borries Demeler Chongwoo A. Kim Jeetain Mittal Nicole J. Francis Montreal Clinical Research Institute (IRCM) Montreal QC Canada Division of Experimental Medicine McGill University Montreal QC Canada Department of Chemistry and Biochemistry The University of Lethbridge Lethbridge AB Canada Artie McFerrin Department of Chemical Engineering Texas A&M University College Station TX USA Department of Biochemistry and Molecular Medicine University of Montreal Montreal QC Canada Department of Biochemistry and Molecular Genetics Midwestern University Glendale AZ USA Department of Chemistry and Biochemistry City College of New York New York NY USA Department of Chemical and Biomedical Engineering University of Wyoming Laramie WY USA Center for Materials Physics and Technology Naval Research Laboratory Washington DC USA Ph.D. Program in Biochemistry The Graduate Center of the City University of New York New York NY USA Ph.D. Program in Biology The Graduate Center of the City University of New York New York NY USA Ph.D. Program in Chemistry The Graduate Center of the City University of New York New York NY USA Department of Chemistry and Biochemistry University of Montana Missoula MT USA Department of Chemistry Texas A&M University College Station TX USA Interdisciplinary Graduate Program in Genetics and Genomics Texas A&M University College Station TX USA

Biomolecular condensates are increasingly recognized as key regulators of chromatin organization, yet how their formation and properties arise from protein sequences remains incompletely understood. Cross-species comparisons can reveal both conserved functions and significant evolutionary differences. Here, we integrate in vitro reconstitution, molecular dynamics simulations, and cell-based assays to examine how Drosophila and human variants of Polyhomeotic (Ph)—a subunit of the PRC1 chromatin regulatory complex—drive condensate formation through their sterile alpha motif (SAM) oligomerization domains. We identify divergent interactions between SAM and the disordered linker connecting it to the rest of Ph. These interactions enhance oligomerization and modulate both the formation and properties of reconstituted condensates. Oligomerization influences condensate dynamics but minimally impacts condensate formation. Linker-SAM interactions also affect condensate formation in Drosophila and human cells and growth in Drosophila imaginal discs. Our findings show how evolutionary changes in disordered linkers can fine-tune condensate properties, providing insights into sequence-function relationships.

关键词： sterile alpha motif oligomerization molecular dynamics simulations phase separation gene regulation Polycomb intrinsically disordered regions biomolecular condensates analytical ultracentrifugation biochemistry CRISPR Drosophila

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Wisdom of Crowds for Supporting the Safety Evaluation of Nanomaterials

SSRN

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SSRN 2025年

作者： Saarimäki, Laura Aliisa Fratello, Michele del Giudice, Giusy Di Lieto, Emanuele Afantitis, Antreas Alenius, Harri Chiavazzo, Eliodoro Gulumian, Mary Karisola, Piia Lynch, Iseult Mancardi, Giulia Melagraki, Georgia Netti, Paolo A. Papadiamantis, Anastasios G. Peijnenburg, Willie Santos, Hélder A. Serchi, Tommaso Shahbazi, Mohammad-Ali Stoeger, Tobias Valsami-Jones, Eugenia Vivo, Paola Vrček, Ivana Vinković Vogel, Ulla Wick, Peter Winkler, David A. Serra, Angela Greco, Dario Faculty of Medicine and Health Technology Tampere University Tampere33520 Finland Division of Pharmaceutical Biosciences Faculty of Pharmacy University of Helsinki Helsinki00790 Finland NovaMechanics Ltd Nicosia Cyprus Institute of Environmental Medicine Karolinska Institutet Stockholm171 77 Sweden Research Program Medical Faculty University of Helsinki Helsinki00290 Finland Politecnico di Torino Corso Duca degli Abruzzi 24 Torino10129 Italy National Institute for Occupational Health National Health Laboratory Services Johannesburg South Africa School of Geography Earth and Environmental Sciences University of Birmingham Birmingham United Kingdom Division of Physical Sciences and Applications Hellenic Military Academy Vari Greece Interdisciplinary Research Centre on Biomaterials-CRIB University of Napoli Federico II P.le Tecchio 80 Napoli80125 Italy Institute of Environmental Sciences Leiden University Leiden Netherlands National Institute of Public Health and the Environment Center for Safety of Products and Substances Bilthoven Netherlands University of Groningen Groningen Netherlands Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki Helsinki Finland Luxembourg Institute of Science and Technology 5 Avenue des Hauts Fourneaux Eschsur-Alzette4362 Luxembourg Munich Germany Solar Cells Faculty of Engineering and Natural Sciences Tampere University P.O. Box 541 TampereFI-33014 Finland Institute for Medical Research and Occupational Health Zagreb Croatia National Research Centre for the Working Environment Copenhagen ODK-2100 Denmark Lerchenfeldstrasse 5 St. Gallen9014 Switzerland La Trobe Institute of Molecular Science La Trobe University Bundoora3086 Australia Monash Institute of Pharmaceutical Sciences Monash University Parkville3052 Australia School of Pharmacy University of Nottingham NottinghamNG7 2QL United Kingdom Tampere Institute for Advanced Study

The development of new approach methodologies (NAMs) to replace current in vivo testing for the safety assessment of engineered nanomaterials (ENMs) is hindered by the scarcity of validated experimental data for a broad range of ENMs. We introduce a framework to address this challenge by harnessing the collective expertise of professionals from multiple complementary and related fields (‘wisdom of crowds’ or WoC). By integrating expert insights, we aim to fill data gaps and generate consensus concern scores for diverse ENMs, thereby enhancing the predictive power of nanosafety computational models. Our investigation reveals an alignment between expert opinion and experimental data, providing robust estimations of concern levels. Building upon these findings, we employ predictive machine learning models trained on the newly defined concern scores, ENM descriptors, and gene expression profiles, to quantify potential harm across various toxicity endpoints. These models further revealed key genes potentially involved in underlying toxicity mechanisms. Notably, genes associated with metal ion homeostasis, inflammation, and oxidative stress emerge as predictors of ENM toxicity across diverse endpoints. This study showcases the value of integrating expert knowledge and computational modeling to address the complexity of nanomaterial safety. Our work suggests that this interdisciplinary approach enhances the accuracy and efficiency of safety assessment in the rapidly evolving landscape of nanotechnology. © 2025, The Authors. All rights reserved.

关键词： Nanoclay

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Complete mitochondrial genome of brownstripe red snapper,Lutjanus vitta(Perciformes: Lutjanidae)

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Mitochondrial DNA Part B 2018年第2期3卷 1129-1130页

作者： Sapto Andriyono Jobaidul Alam Dong Hee Kwak Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Fisheries and Marine Faculty Universitas Airlangga East Java Indonesia Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

The complete mitochondrial genome of the brownstripe red snapper,Lutjanus vittawas determined by MiSeq sequencing platform. The mitogenome ofL. vitta(16,498 bp) encoded the typical 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two non-coding regions (origin of light strand replication; OLandD-Loopcontrol region; CR). Phylogenetic analysis based on the full mitochondrial genome sequences showed thatL. vittais most closely related toL. russellii. The complete mitogenome sequence ofL. vittawould provide the information of the genetic biodiversity inLutjanusfishes, which would be further used for their scientific management in Indonesian waters.

关键词： Next generation sequencing Lutjanus vitta mitogenome snapper Indonesia

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Complete mitochondrial genome ofPenaeus acehensis(Crustacea, Decapoda, Penaeidae) from Aceh province, Indonesia

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Mitochondrial DNA Part B 2018年第2期3卷 898-899页

作者： Sinar Pagi Sektiana M. Tahang Sapto Andriyono Jobaidul Alam Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaAquaculture Technology Study Program Sekolah Tinggi Perikanan Jakarta Indonesia Brackishwater Aquaculture Development Center Aceh Indonesia Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaFisheries and Marine Faculty Universitas Airlangga Surabaya Indonesia Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

Penaeid shrimps are widely distributed from Indian to western Pacific Oceans and some which are economically important. In this study, we reported full mitochondrial genome of an endemic shrimp species,Penaeus acehensis, which inhabits exclusively in the coastal water of Aceh, Indonesia. Full length of circular mitogenome ofP. acehensiswas 15,991 bp in length, which contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. Start codons of all protein-coding genes were ATN except for COX1 in which ACG was used. Incomplete stop codon (T- -) was found in five genes including COX2, COX3, NAD5, NAD4, and NAD4L. Among its relatives,P. acehensiswas most closely related toPenaeus monodonshowing 89% sequence identity in its mitogenome, which was corresponding to morphological analysis. Phylogenetic tree result showed thatP. acehensiswas clustered together with those were distributed in Indo-West Pacific region (clade II), which is distinct from Eastern Pacific region (clade I).

关键词： Mitogenome Dendrobranchiata next-generation sequencing shrimp Indonesia

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Time synchronization between parietal–frontocentral connectivity with MRCP and gait in post-stroke bipedal tasks

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Journal of Neuroengineering and Rehabilitation 2024年第1期21卷 101页

作者： Phang, Chun-Ren Su, Kai-Hsiang Cheng, Yuan-Yang Chen, Chia-Hsin Ko, Li-Wei International Ph.D. Program in Interdisciplinary Neuroscience (UST) College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biological Science and Technology College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Physical Medicine and Rehabilitation Taichung Veterans General Hospital Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Department of Physical Medicine and Rehabilitation Kaohsiung Medical University Hospital Kaohsiung Taiwan School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Regenerative Medicine and Cell Therapy Research Center Kaohsiung Medical University Kaohsiung Taiwan Institute of Electrical and Control Engineering National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biomedical Science and Environment Biology Kaohsiung Medical University Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan

Background: In post-stroke rehabilitation, functional connectivity (FC), motor-related cortical potential (MRCP), and gait activities are common measures related to recovery outcomes. However, the interrelationship between FC, MRCP, gait activities, and bipedal distinguishability have yet to be investigated. Methods: Ten participants were equipped with EEG devices and inertial measurement units (IMUs) while performing lower limb motor preparation (MP) and motor execution (ME) tasks. MRCP, FCs, and bipedal distinguishability were extracted from the EEG signals, while the change in knee degree during the ME phase was calculated from the gait data. FCs were analyzed with pairwise Pearson’s correlation, and the brain-wide FC was fed into support vector machine (SVM) for bipedal classification. Results: Parietal–frontocentral connectivity (PFCC) dysconnection and MRCP desynchronization were related to the MP and ME phases, respectively. Hemiplegic limb movement exhibited higher PFCC strength than nonhemiplegic limb movement. Bipedal classification had a short-lived peak of 75.1% in the pre-movement phase. These results contribute to a better understanding of the neurophysiological functions during motor tasks, with respect to localized MRCP and nonlocalized FC activities. The difference in PFCCs between both limbs could be a marker to understand the motor function of the brain of post-stroke patients. Conclusions: In this study, we discovered that PFCCs are temporally dependent on lower limb gait movement and MRCP. The PFCCs are also related to the lower limb motor performance of post-stroke patients. The detection of motor intentions allows the development of bipedal brain-controlled exoskeletons for lower limb active rehabilitation. © The Author(s) 2024.

关键词： Brain–computer interface Functional connectivity Motor execution Motor preparation Post-stroke

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The complete mitochondrial genome of the Argentine red shrimpPleoticus muelleri(Bate, 1888) (Crustacea, Decapoda, Solenoceridae)

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Mitochondrial DNA Part B 2018年第2期3卷 1027-1028页

作者： Nack-Keun Kim Jobaidul Alam Gyung Ryul Kim Sapto Andriyono Hyun Park Hyun-Woo Kim Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaFisheries and Marine Faculty Universitas Airlangga Surabaya Indonesia Korea Polar Research Institute Korea Ocean Research and Development Institute Incheon Republic of Korea Interdisciplinary Program of Biomedical Mechanical and Electrical Engineering Pukyong National University Busan Republic of KoreaDepartment of Marine Biology Pukyong National University Busan Republic of Korea

The complete mitochondrial genome of Argentine red shrimp,Pleoticus muelleri(Bate, 1888) was determined using the MiSeq platform. Its mitogenome (16,189 bp) encoded the canonical 13 protein-coding genes, 22 tRNA genes, two rRNA genes. Start codons of all protein-coding genes were ATN except for ATP8, while incomplete stop codons (T–) were identified in six genes including COXI, COXII, COXIII, NAD3, NAD5, and NAD6. The mitogenome ofP. muellerishowed highest sequence identity withParapenaeopsis hardwickii(82%) andSolenocera crassicornis(81%). Phylogenetic analysis showed three shrimps in Solenoceridae includingP. muelleriwere grouped together from those in Penaeidae, which suggests taxonomic reexamination for those in those family.

关键词： Next generation sequencing Pleoticus muelleri mitochondrial genome decapod phylogeny

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Author Correction: O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine

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Nature communications 2022年第1期13卷 6253页

作者： Kibum Kim Hee Chan Yoo Byung Gyu Kim Sulhee Kim Yulseung Sung Ina Yoon Ya Chun Yu Seung Joon Park Jong Hyun Kim Kyungjae Myung Kwang Yeon Hwang Sunghoon Kim Jung Min Han Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School Yonsei University Seoul 03722 South Korea. Yonsei Institute of Pharmaceutical Sciences College of Pharmacy Yonsei University Incheon 21983 South Korea. Center for Genomic Integrity Institute for Basic Science Ulsan 44919 South Korea. Department of Biotechnology College of Life Sciences and Biotechnology Korea University Seoul 02841 South Korea. Institute for Artificial Intelligence and Biomedical Research Medicinal Bioconvergence Research Center Yonsei University Incheon 21983 South Korea. College of Medicine Gangnam Severance Hospital Yonsei University Seoul 06273 South Korea. Department of Biochemistry School of Medicine Catholic University of Daegu Daegu 42472 South Korea. Department of Biomedical Engineering Ulsan National Institute of Science and Technology Ulsan 44919 South Korea. Interdisciplinary Program of Integrated OMICS for Biomedical Science Graduate School Yonsei University Seoul 03722 South Korea. jhan74@yonsei.ac.kr. Yonsei Institute of Pharmaceutical Sciences College of Pharmacy Yonsei University Incheon 21983 South Korea. jhan74@yonsei.ac.kr. POSTECH Biotech Center Pohang University of Science and Technology Pohang 37673 South Korea. jhan74@yonsei.ac.kr.

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Interpretable network propagation with application to expanding the repertoire of human proteins that interact with SARS-CoV-2

arXiv

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arXiv 2020年

作者： Law, Jeffrey N. Akers, Kyle Tasnina, Nure Della Santina, Catherine M. Deutsch, Shay Kshirsagar, Meghana Klein-Seetharaman, Judith Crovella, Mark Rajagopalan, Padmavathy Kasif, Simon Murali, T.M. Interdisciplinary Ph.D. Program in Genetics Bioinformatics and Computational Biology BlacksburgVA United States Department of Computer Science Virginia Tech BlacksburgVA United States Department of Biomedical Engineering Boston University BostonMA United States Department of Mathematics University of California Los AngelesCA United States AI for Good Lab Microsoft RedmondWA United States Department of Chemistry Colorado School of Mines GoldenCO United States Department of Computer Science Boston University BostonMA United States Department of Chemical Engineering Virginia Tech BlacksburgVA United States

Background: Network propagation has been widely used for nearly 20 years to predict gene functions and phenotypes. Despite the popularity of this approach, little attention has been paid to the question of provenance tracing in this context, e.g., determining how much any experimental observation in the input contributes to the score of every prediction. Results: We design a network propagation framework with two novel components and apply it to predict human proteins that directly or indirectly interact with SARS-CoV-2 proteins. First, we trace the provenance of each prediction to its experimentally validated sources, which in our case are human proteins experimentally determined to interact with viral proteins. Second, we design a technique that helps to reduce the manual adjustment of parameters by users. We find that for every top-ranking prediction, the highest contribution to its score arises from a direct neighbor in a human protein-protein interaction network. We further analyze these results to develop functional insights on SARS-CoV-2 that expand on known biology such as the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. Conclusions: We examine how our provenance tracing method can be generalized to a broad class of network-based algorithms. We provide a useful resource for the SARS-CoV-2 community that implicates many previously undocumented proteins with putative functional relationships to viral infection. This resource includes potential drugs that can be opportunistically repositioned to target these proteins. We also discuss how our overall framework can be extended to other, newly-emerging viruses. © 2020, CC BY-NC-SA.

关键词： SARS

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Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three-Dimensional Hydrogels

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Current Protocols in Stem Cell Biology 2019年第1期51卷 e97页

作者： Balikov, Daniel A. Lippmann, Ethan S. Bellan, Leon M. Department of Mechanical Engineering Vanderbilt University Nashville TN United States Interdisciplinary Materials Science Program Vanderbilt University Nashville TN United States Department of Biomedical Engineering Vanderbilt University Nashville TN United States Department of Chemical and Biomolecular Engineering Vanderbilt University Nashville TN United States

Morphogens are biological molecules that alter cellular identity and behavior across both space and time. During embryonic development, morphogen spatial localization can be confined to small volumes in a single tissue or permeate throughout an entire organism, and the temporal effects of morphogens can range from fractions of a second to several days. In most cases, morphogens are presented as a gradient to adjacent cells within tissues to pattern cell fate. As such, to appropriately model development and build representative multicellular architectures in vitro, it is vital to recapitulate these gradients during stem cell differentiation. However, the ability to control morphogen presentation within in vitro systems remains challenging. Here, we describe an innovative platform using channels patterned within thick, three-dimensional hydrogels that deliver multiple morphogens to embedded cells, thereby demonstrating exquisite control over both spatial and temporal variations in morphogen presentation. This generalizable approach should have broad utility for researchers interested in patterning in vitro tissue structures. © 2019 by John Wiley & Sons, Inc. © 2019 John Wiley & Sons, Inc.

关键词： differentiation gradient hydrogel morphogen stem cell tissue engineering

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High Affinity to Skeleton Rare Earth Doped Nanoparticles for Near-Infrared Ⅱ Imaging

High Affinity to Skeleton Rare Earth Doped Nanoparticles for...

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第十一届全国化学生物学学术会议

作者：和树庆 Changfeng Wu Junle Qu Zhen Cheng 南方科技大学 Academy for Advanced Interdisciplinary Studies and Department of Biomedical Engineering Southern University of Science and Technology(SUSTech) Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Optoelectronic EngineeringShenzhen University Molecular Imaging Program at Stanford(MIPS) Bio-X Programand Department of RadiologyCanary Center at Stanford for Cancer Early DetectionStanford University

As a newly non-invasive emerging modality,NIR-Ⅱ fluorescence imaging(1000-1700 nm) has many advantages over conventional visible and NIR-I imaging(700-900 nm).[1-5] Unfortunately,few NIR-Ⅱ fluorophores are suitable for bone ***,we report an NIR-Ⅱ fluorophore based on DSPE-mPEG encapsulated rare earth doped nanoparticles(RENPs@DSPE-mPEG),which shows inherent affinity to bone without linking any targeting ligands,and thus it provides an alternative non-invasive and non-radiation strategy for skeletal system mapping and bone diseases ***,within NIR-Ⅱ window,imaging at longer wavelength(1345 nm) provides higher resolution and signal-to-noise ratio than that imaging at 1064 nm,even though quantum yield at 1064 nm is 2-fold higher than that at 1345 nm.[2] Besides bone imaging,RENPs@DSPE-mPEG show imaging application in blood vessel and lymph ***,RENPs@DSPE-mPEG can be internalized by circulating white blood *** finding may open a window to increase efficient nanoparticle delivery in the fields such as immunotherapy and improve the diagnostic and therapeutic efficacy of cancer-targeted nanoparticles in clinical applications.

关键词： NIR-Ⅱ imaging NIR-Ⅱa imaging Bone imaging Rare earth doped nanoparticles Thrombus

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