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Priority Screening of Contaminants of Emerging Concern (Cecs) in Surface Water: Comparing Cell-Based Bioassays and Exposure-Activity Ratios (Ears)

SSRN

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SSRN 2024年

作者： Heuvel, John Patrick Vanden Granda, Megan Ferguson, Francesca M. Glaberman, Scott R. Preisendanz, Heather E. Department of Veterinary and Biomedical Sciences Penn State University University ParkPA United States INDIGO Biosciences Inc. 3006 Research Drive State CollegePA16801 United States Institute for Sustainable Agricultural Food and Environmental Science The Pennsylvania State Univ. University ParkPA16802 United States Intercollege Graduate Degree Program in Ecology Penn State University University ParkPA United States Department of Entomology Penn State University University ParkPA United States Department of Agricultural and Biological Engineering Penn State University University ParkPA United States George Mason University Department of Environmental Science and Policy FairfaxVA United States Department of Veterinary and Biomedical Sciences Penn State University 122 Agricultural Sciences and Industry Building University ParkPA16802 United States

In this study, we compared a wide range of cell-based bioassays to the use of chemical analysis followed by exposure-activity ratio (EAR) and Toxicological Prioritization index (ToxPi) for prioritizing chemicals, sites, and hazard concerns in water samples. Surface water samples were collected from nine sites in three Central Pennsylvania streams and analyzed for a targeted list of compounds of emerging concern (CECs), including pesticides, personal care products, and pharmaceuticals. Cell-based reporter assays evaluated human and zebrafish molecular initiating events (MIEs) in endocrine and metabolic disruption, altered lipid metabolism, and oxidative stress. Bioassays showed that 29 out of 40 assays had at least one site with activity over the limit of detection. The receptors that exhibited the highest number of samples above the effect-based trigger (EBT) values that would be expected to cause toxicity were Aryl hydrocarbon receptor (AhR, human and zebrafish), Pregnane X Receptor (PXR), Estrogen Receptor-beta (ERB), and Androgen Receptor (AR). Characterizing the collection sites by their bioactivity aligned closely with the stream in which samples were collected, with the three sites in Warriors Mark Run, three in Halfmoon, and three in Spruce Run more similar than sites from the other streams. The sum of all EARs for each chemical indicated that the pharmaceutical Carbamazepine and the pesticides Carbaryl and Atrazine posed the greatest concern. However, predicted activity and site prioritization based on individual chemical analysis and calculated EAR were different than those measured by bioassay, indicating that biologically active chemicals are present in the samples that were not included in the targeted analytes. Taken together, these data show that chemical analysis and EAR analysis are beneficial for prioritization of chemicals, whereas mechanism-based bioassays are more inclusive of known as well as unknown chemical contaminants and thus of more use fo

关键词： Water quality

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Electron Tomography Finds Three-Dimensional Chromatin Packing Domain Structure in Single Cell Different from Topological Associated Domains

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Microscopy and Microanalysis 2024年第SUPPLEMENT_1期30卷

作者： Li, Wing Shun Carter, Lucas Almassalha, Luay Pujadas, Emily Carignano, Marcelo Bleher, Reiner dos Reis, Roberto Backman, Vadim Dravid, Vinayak Applied Physics Program Northwestern University Evanston IL USA Department of Biomedical Engineering Northwestern University Evanston IL USA IBIS Interdisciplinary Biological Sciences Graduate Program Northwestern University Evanston IL USA Department of Materials Sciences and Engineering Northwestern University Evanston IL USA Northwestern University Atomic and Nanoscale Characterization Experimental (NUANCE) Center Northwestern University Evanston IL USA International Institute of Nanotechnology Northwestern University Evanston IL USA

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Artifact Removal in tACS-EEG Recordings: A Combined Methodology Based on the Empirical Wavelet Transform*

Artifact Removal in tACS-EEG Recordings: A Combined Methodol...

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Annual International Conference of the IEEE engineering in Medicine and Biology Society (EMBC)

作者： Xuanteng Yan Marie-Hélène Boudrias Georgios D. Mitsis Graduate Program in Biological and Biomedical Engineering McGill University Montréal Canada School of Physical & Occupational Therapy McGill University Montréal Canada Department of Bioengineering McGill University Montréal Canada

ISBN: (数字)9781728119908

ISBN: (纸本)9781728119915

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that modulates brain activity, which yields promise for achieving desired behavioral outcomes in different contexts. Combining tACS with electroencephalography (EEG) allows for the monitoring of the real-time effects of stimulation. However, the EEG signal recorded with simultaneous tACS is largely contaminated by stimulation-induced artifacts. In this work, we examine the combination of the empirical wavelet transform (EWT) with three blind source separation (BSS) methods: principal component analysis (PCA), multiset canonical correlation analysis (MCCA) and independent vector analysis (IVA), aiming to remove artifacts in tACS-contaminated EEG recordings. Using simulated data, we show that EWT followed by IVA achieves the best performance. Using experimental data, we show that BSS combined with EWT performs better compared to standard BSS methodology in terms of preserving useful information while eliminating artifacts.

关键词： Electroencephalography Tensile stress Principal component analysis Correlation Time series analysis Wavelet transforms

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CCL5 Protects Cortical Neuron Function by Regulating M2 Microglia Activation After Mild Traumatic Brain Injury

SSRN

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SSRN 2022年

作者： Tsai, Yih-Jeng Ho, Man-Hau Yen, Chia-Hung Wang, Jia-Yi Burnouf, Thierry Chen, Chia-Yen Wang, Yun Chiang, Yung-Hsiao Hoffer, Barry J. Chou, Szu-Yi Department of Otolaryngology Head and Neck Surgery Shin Kong Wu HoSu Memorial Hospital Taipei Taiwan School of Medicine Fu Jen Catholic University New Taipei City Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University National Health Research Institute Taiwan Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Biological Science and Technology National Pingtung University of Science and Technology Neipu Pingtung91201 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Neurosurgery Taipei Medical University Hospital Taipei11031 Taiwan Neuroscience Research Center Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan NeuroTMULille International Laboratory Taipei Medical University Taipei Taiwan International PhD Program in Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Brain and Consciousness Research Centre TMU Shuang Ho Hospital New Taipei City Taiwan Center for Neuropsychiatric Research National Health Research Institutes Zhunan Miaoli County Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University 11031 Taiwan Department of Neurosurgery Case Western Reserve University School of Medicine ClevelandOH United States Scientist Emeritus National Institutes of Health United States International Master Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Cytokines and chemokines play important roles in inflammation and repair following brain injury. M1 microglia are pro-inflammatory which produce cytokines and lead to neural injury;in contrast, M2 microglia are anti-inflammatory, release neurotrophic factors, and promote neural repair processes. Chemokine CCL5, increased after TBI, shows a neuroprotective function by reducing oxidative stress. CCL5 may contribute to the balance between oxidative stress and immune responses after brain injury. Herein, we investigated the role of CCL5 in microglial polarization after mild traumatic brain injury, focusing on the cerebral cortex.C57BL/6 and CCL5 knockout (CCL5-KO) mice were given a mild traumatic brain injury (TBI) using weight-drop. Neurological parameters such as motor and sensory functions were analyzed by mNSS score, accelerating rotarod, beam walking, and adhesive removal tests. Oxidative stress and neuron damage were measured by NADPH oxidase activity, hypoxyloprobe staining and FJC. Performance of motor and sensory functions in both WT and CCL5-KO mice were impaired after brain injury which recovered after 7 days-post-injury (dpi) in the WT group but only after 14 days in the CCL5-KO mouse group. RT-qPCR analysis revealed that pro-inflammation cytokines - IL-1β, TNF-α, and IL-6 were higher in CCL5-KO mice compared to WT mice at 4 and 14 dpi. In contrast, M2-like microglia markers - IL-10 and Agr-1 were increased in WT mouse cortical tissue at 4 dpi. Oxidative stress increased both M1 and M2- related cytokine expression in BV2 cells treated with H 2 O 2;CCL5 treatment increased M2- but suppressed M1- related cytokine gene activation. Intranasal delivery of CCL5 reduced neuronal oxidative stress, increased IL-10 expression and improved motor and sensory functions in CCL5-KO mice after brain *** summary, CCL5, which alters immune responses and protects neurons from TBI damage, has an important function in regulating M2-like microglial polarization during post-

关键词： Polarization

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Advances in transcription factor delivery: Target selection, engineering strategies, and delivery platforms

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Journal of Controlled Release 2025年 384卷 113885页

作者： Lee, Yeji Yoo, Seongkyeong Cho, Seongeon Kim, Iljin Kim, In-San KU-KIST Graduate School of Converging Science and Technology Korea University Seoul02841 Korea Republic of Chemical and Biological Integrative Research Center Biomedical Research Institute Korea Institute Science and Technology Seoul02792 Korea Republic of Department of Pharmacology and Program in Biomedical Science and Engineering Inha University College of Medicine Incheon22212 Korea Republic of Research Center for Controlling Intercellular Communication Inha University College of Medicine Incheon22212 Korea Republic of

Recent advances in delivery systems for transcription factors (TFs) have opened new therapeutic opportunities in regenerative medicine, cancer therapy, and genetic disorders. However, effective TF delivery still faces substantial obstacles, including limited cellular uptake, inefficient nuclear translocation, low cargo stability, and insufficient target specificity. Furthermore, artificial TFs have enabled targeted modulation of gene expression, further expanding their therapeutic potential. This review comprehensively discusses current progress in TF delivery methodologies, including direct TF protein delivery using cell-penetrating peptides, and extracellular vesicles, as well as TF gene delivery approaches utilizing both lipid-based nanoparticles and viral strategies. Notably, engineered nanoparticles have emerged as promising platforms due to their precise control over TF delivery, improved specificity, and minimized off-target effects. Despite these significant advancements, major hurdles in delivery efficiency, cargo stability, and overall safety persist. Overcoming these obstacles will be essential to accelerate the clinical translation of TF-based therapeutics for a broad spectrum of diseases. © 2024

关键词： Transcription factors

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Uncovering diffusive states of the yeast proton pump, Pma1, and how labeling method can change diffusive behavior

arXiv

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arXiv 2022年

作者： Bailey, Mary Lou P. Pratt, Susan E. Zhang, Yongdeng Hinrichsen, Michael Bewersdorf, Joerg Regan, Lynne J. Mochrie, Simon G.J. Integrated Graduate Program in Physical and Engineering Biology Yale University New HavenCT06511 United States Department of Applied Physics Yale University New HavenCT06511 United States Department of Physics Yale University New HavenCT06511 United States Department of Cell Biology Yale University New HavenCT06511 United States Department of Biomedical Engineering Yale University New HavenCT06511 United States Institute of Quantitative Biology Biochemistry and Biotechnology Center for Synthetic and Systems Biology School of Biological Sciences University of Edinburgh Edinburgh06511 United Kingdom

We present and analyze video-microscopy-based single-particle-tracking measurements of the budding yeast (Saccharomyces cerevisiae) membrane protein, Pma1, fluorescently-labeled either by direct fusion to the switchable fluorescent protein, mEos3.2, or by a novel, light-touch, labeling scheme, in which a 5 amino acid tag is directly fused to the C-terminus of Pma1, which then binds mEos3.2. The diffusivity distributions of these two populations of single particle tracks differ significantly, demonstrating that labeling method can be an important determinant of diffusive behavior. We also applied perturbation expectation maximization (pEMv2) [Physical Review E 94, 052412 (2016)], which sorts trajectories into the statistically-optimum number of diffusive states. For both TRAP-labeled Pma1 and Pma1-mEos3.2, pEMv2 sorts the tracks into two diffusive states: an essentially immobile state and a more mobile state. However, the mobile fraction of Pma1-mEos3.2 tracks is much smaller (∼ 0.1) than the mobile fraction of TRAP-labeled Pma1 tracks (∼ 0.5). In addition, the diffusivity of Pma1-mEos3.2's mobile state is several times smaller than the diffusivity of TRAP-labeled Pma1's mobile state. To critically assess pEMv2's performance, we compare the diffusivity and covariance distributions of the experimental pEMv2-sorted populations to corresponding theoretical distributions, assuming that Pma1 displacements realize a Gaussian random process. The experiment-theory comparisons for both the TRAP-labeled Pma1 and Pma1-mEos3.2 reveal good agreement, bolstering the pEMv2 approach. © 2022, CC BY.

关键词： Diffusion

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Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2

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Nature Communications 2023年第1期14卷 311-311页

作者： Huang, Kuan-Ying A. Chen, Xiaorui Mohapatra, Arpita Nguyen, Hong Thuy Vy Schimanski, Lisa Tan, Tiong Kit Rijal, Pramila Vester, Susan K. Hills, Rory A. Howarth, Mark Keeffe, Jennifer R. Cohen, Alexander A. Kakutani, Leesa M. Wu, Yi-Min Shahed-Al-Mahmud, Md Chou, Yu-Chi Bjorkman, Pamela J. Townsend, Alain R. Ma, Che Graduate Institute of Immunology and Department of Pediatrics National Taiwan University Hospital College of Medicine National Taiwan University Taipei Taiwan Genomics Research Center Academia Sinica Taipei Taiwan College of Medicine Chang Gung University Taoyuan Taiwan Chemical Biology and Molecular Biophysics program Taiwan International Graduate Program Academia Sinica Taipei Taiwan Institute of Biochemical Sciences National Taiwan University Taipei Taiwan MRC Human Immunology Unit Weatherall Institute of Molecular Medicine University of Oxford John Radcliffe Hospital Oxford United Kingdom Department of Biochemistry University of Oxford Oxford OX1 3QU United Kingdom Division of Biology and Biological Engineering California Institute of Technology Pasadena United States Institute of Biological Chemistry Academia Sinica Taipei 11529 Taiwan Biomedical Translation Research Center Academia Sinica Taipei 11529 Taiwan Department of Pharmacology University of Cambridge Tennis Court Road Cambridge CB2 1PD United Kingdom

Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the “down” state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses. We observed a continuum of partially overlapping antibody epitopes from lower to upper part of the inner face of the RBD and some antibodies extend towards the receptor-binding motif. The majority of antibodies are substantially compromised by three mutational hotspots (S371L/F, S373P and S375F) in the lower part of the Omicron BA.1, BA.2 and BA.4/5 RBD. By contrast, antibody IY-2A induces a partial unfolding of this variable region and interacts with a conserved conformational epitope to tolerate all antigenic variations and neutralize diverse sarbecoviruses as well. This finding establishes that antibody recognition is not limited to the normal surface structures on the RBD. In conclusion, the delineation of functionally and structurally conserved RBD epitopes highlights potential vaccine and therapeutic candidates for COVID-19. © 2023, The Author(s).

关键词： Antibodies SARS-CoV-2

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The mitochondrial genome data of the Capsicum annuum cv. Dempsey (Solanaceae)

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Data in Brief 2025年 60卷

作者： Seona Yun Junseong Bae Jeongbin Park Hyeran Kim Institute of Life Sciences Kangwon National University Chuncheon Republic of Korea Interdisciplinary Program of Genomic Data Science Pusan National University Yangsan Republic of Korea Graduate School of Medical AI Pusan National University Yangsan Republic of Korea School of Biomedical Convergence Engineering Pusan National University Yangsan Republic of Korea Department of Biological Sciences Kangwon National University Chuncheon Republic of Korea

Capsicum annuum L. (1753), commonly known as pepper, holds significant economic value as one of the globally cultivated horticultural crops. This study presents the mitochondrial genome of the sweet pepper C. annuum cv. Dempsey, assembled using Illumina NovaSeq data. The circular mitogenome is 577,453 base pairs (bp) in length and includes 36 protein-coding genes, three ribosomal RNA genes, and 43 transfer RNA genes. Phylogenetic analysis reveals that C. annuum is not monophyletic, with C. annuum cv. Dempsey identified as a sister to the hot pepper C. annuum cv. Jeju. This study provides as a valuable resource for comparative analyses of pepper mitogenomes, enhancing our understanding of the evolution and adaptive mechanisms of pepper species.

关键词： Capsicum annuum Sweet pepper Cultivar dempsey Mitogenome Phylogeny

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A consensus protocol for functional connectivity analysis in the rat brain (vol 26, pg 673, 2023)

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NATURE NEUROSCIENCE 2023年第6期26卷 1127-1128页

作者： Grandjean, Joanes Desrosiers-Gregoire, Gabriel Anckaerts, Cynthia Angeles-Valdez, Diego Ayad, Fadi Barriere, David A. Blockx, Ines Bortel, Aleksandra Broadwater, Margaret Cardoso, Beatriz M. Celestine, Marina Chavez-Negrete, Jorge E. Choi, Sangcheon Christiaen, Emma Clavijo, Perrin Colon-Perez, Luis Cramer, Samuel Daniele, Tolomeo Dempsey, Elaine Diao, Yujian Doelemeyer, Arno Dopfel, David Dvorakova, Lenka Falfan-Melgoza, Claudia Fernandes, Francisca F. Fowler, Caitlin F. Fuentes-Ibanez, Antonio Garin, Clement M. Gelderman, Eveline Golden, Carla E. M. Guo, Chao C. G. Henckens, Marloes J. A. G. Hennessy, Lauren A. Herman, Peter Hofwijks, Nita Horien, Corey Ionescu, Tudor M. Jones, Jolyon Kaesser, Johannes Kim, Eugene Lambers, Henriette Lazari, Alberto Lee, Sung-Ho Lillywhite, Amanda Liu, Yikang Liu, Yanyan Y. Lopez-Castro, Alejandra Lopez-Gil, Xavier Ma, Zilu MacNicol, Eilidh Madularu, Dan Mandino, Francesca Marciano, Sabina McAuslan, Matthew J. McCunn, Patrick McIntosh, Alison Meng, Xianzong Meyer-Baese, Lisa Missault, Stephan Moro, Federico Naessens, Daphne M. P. Nava-Gomez, Laura J. Nonaka, Hiroi Ortiz, Juan J. Paasonen, Jaakko Peeters, Lore M. Pereira, Mickael Perez, Pablo D. Pompilus, Marjory Prior, Malcolm Rakhmatullin, Rustam Reimann, Henning M. Reinwald, Jonathan Del Rio, Rodrigo Triana Rivera-Olvera, Alejandro Ruiz-Perez, Daniel Russo, Gabriele Rutten, Tobias J. Ryoke, Rie Sack, Markus Salvan, Piergiorgio Sanganahalli, Basavaraju G. Schroeter, Aileen Seewoo, Bhedita J. Selingue, Erwan Seuwen, Aline Shi, Bowen Sirmpilatze, Nikoloz Smith, Joanna A. B. Smith, Corrie Sobczak, Filip Stenroos, Petteri J. Straathof, Milou Strobelt, Sandra Sumiyoshi, Akira Takahashi, Kengo Torres-Garcia, Maria E. Tudela, Raul van den Berg, Monica van der Marel, Kajo van Hout, Aran T. B. Vertullo, Roberta Vidal, Benjamin Vrooman, Roel M. Wang, Victora X. Wank, Isabel Watson, David J. G. Yin, Ting Zhang, Yongzhi Zurbruegg, Stefan Achard, Sophie Alcauter, Sarael Auer, Dorothee P. Barbier, Emmanuel L. Baudewig, Juergen Beckmann, Chri Donders Institute for Brain Behaviour and Cognition Radboud University Nijmegen The Netherlands Department for Medical Imaging Radboud University Medical Center Nijmegen The Netherlands Cerebral Imaging Centre Douglas Mental Health University Institute Verdun QC Canada Integrated Program in Neuroscience McGill University Montreal QC Canada Bio-imaging Lab University of Antwerp Antwerp Belgium µNEURO Research Centre of Excellence University of Antwerp Antwerp Belgium Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro Mexico Biological and Biomedical Engineering McGill University Montreal QC Canada McConnell Brain Imaging Centre McGill University Montreal QC Canada Montreal Neurological Institute McGill University Montreal QC Canada UMR INRAE/CNRS 7247 Physiologie des Comportements et de la Reproduction Physiologie de la reproduction et des comportements Centre de recherche INRAE de Nouzilly Tours France Department of Neurology and Neurosurgery McGill University Montreal QC Canada Center for Animal MRI University of North Carolina at Chapel Hill Chapel Hill NC USA Department of Neurology University of North Carolina at Chapel Hill Chapel Hill NC USA Biomedical Research Imaging Center University of North Carolina at Chapel Hill Chapel Hill NC USA Preclinical MRI Champalimaud Research Champalimaud Centre for the Unknown Lisbon Portugal Laboratoire des Maladies Neurodégénératives Molecular Imaging Research Center (MIRCen) Université Paris-Saclay Commissariat à l’Énergie Atomique et aux Énergies Alternatives (CEA) CNRS Fontenay-aux-Roses France Departamento de Neurobiología Conductual y Cognitiva Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro México Translational Neuroimaging and Neural Control Group High-Field Magnetic Resonance Max Planck Institute for Biological Cybernetics Tuebingen Germany Graduate Training Centre of Neuroscience International Max

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.

关键词： Databases Neural circuits

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Closing the loop on crowdsourced science

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Proceedings of the National Academy of Sciences of the United States of America 2022年第25期119卷 e2205897119页

作者： James M Robson Alexander A Green Department of Biomedical Engineering Boston University Boston MA 02215. Biological Design Center Boston University Boston MA 02215. Molecular Biology Cell Biology & Biochemistry Program Graduate School of Arts and Sciences Boston University Boston MA 02215.

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