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  1. Article ; Online: Genomic characterization and therapeutic utilization of IL-13-responsive sequences in asthma

    Kyung Duk Koh / Luke R. Bonser / Walter L. Eckalbar / Ofer Yizhar-Barnea / Jiangshan Shen / Xiaoning Zeng / Kirsten L. Hargett / Dingyuan I. Sun / Lorna T. Zlock / Walter E. Finkbeiner / Nadav Ahituv / David J. Erle

    Cell Genomics, Vol 3, Iss 1, Pp 100229- (2023)

    2023  

    Abstract: Summary: Epithelial responses to the cytokine interleukin-13 (IL-13) cause airway obstruction in asthma. Here we utilized multiple genomic techniques to identify IL-13-responsive regulatory elements in bronchial epithelial cells and used these data to ... ...

    Abstract Summary: Epithelial responses to the cytokine interleukin-13 (IL-13) cause airway obstruction in asthma. Here we utilized multiple genomic techniques to identify IL-13-responsive regulatory elements in bronchial epithelial cells and used these data to develop a CRISPR interference (CRISPRi)-based therapeutic approach to downregulate airway obstruction-inducing genes in a cell type- and IL-13-specific manner. Using single-cell RNA sequencing (scRNA-seq) and acetylated lysine 27 on histone 3 (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) in primary human bronchial epithelial cells, we identified IL-13-responsive genes and regulatory elements. These sequences were functionally validated and optimized via massively parallel reporter assays (MPRAs) for IL-13-inducible activity. The top secretory cell-selective sequence from the MPRA, a novel, distal enhancer of the sterile alpha motif pointed domain containing E-26 transformation-specific transcription factor (SPDEF) gene, was utilized to drive CRISPRi and knock down SPDEF or mucin 5AC (MUC5AC), both involved in pathologic mucus production in asthma. Our work provides a catalog of cell type-specific genes and regulatory elements involved in IL-13 bronchial epithelial response and showcases their use for therapeutic purposes.
    Keywords enhancer ; IL-13 ; cell-specific ; CRISPRi ; HBEC ; SPDEF ; Genetics ; QH426-470 ; Internal medicine ; RC31-1245
    Subject code 572
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Use antibiotics in cell culture with caution

    Ann H. Ryu / Walter L. Eckalbar / Anat Kreimer / Nir Yosef / Nadav Ahituv

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    genome-wide identification of antibiotic-induced changes in gene expression and regulation

    2017  Volume 9

    Abstract: Abstract Standard cell culture guidelines often use media supplemented with antibiotics to prevent cell contamination. However, relatively little is known about the effect of antibiotic use in cell culture on gene expression and the extent to which this ... ...

    Abstract Abstract Standard cell culture guidelines often use media supplemented with antibiotics to prevent cell contamination. However, relatively little is known about the effect of antibiotic use in cell culture on gene expression and the extent to which this treatment could confound results. To comprehensively characterize the effect of antibiotic treatment on gene expression, we performed RNA-seq and ChIP-seq for H3K27ac on HepG2 cells, a human liver cell line commonly used for pharmacokinetic, metabolism and genomic studies, cultured in media supplemented with penicillin-streptomycin (PenStrep) or vehicle control. We identified 209 PenStrep-responsive genes, including transcription factors such as ATF3 that are likely to alter the regulation of other genes. Pathway analyses found a significant enrichment for “xenobiotic metabolism signaling” and “PXR/RXR activation” pathways. Our H3K27ac ChIP-seq identified 9,514 peaks that are PenStrep responsive. These peaks were enriched near genes that function in cell differentiation, tRNA modification, nuclease activity and protein dephosphorylation. Our results suggest that PenStrep treatment can significantly alter gene expression and regulation in a common liver cell type such as HepG2, advocating that antibiotic treatment should be taken into account when carrying out genetic, genomic or other biological assays in cultured cells.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes.

    Jose L Lopez / Joel L Ramirez / Tuan Anh Phu / Phat Duong / Laura Bouchareychas / Christina R Kuhrau / Pei-Yu Lin / Walter L Eckalbar / Andrea J Barczak / Joshua D Rudolph / Lenka Maliskova / Michael S Conte / Shant M Vartanian / Robert L Raffai / Adam Z Oskowitz

    PLoS ONE, Vol 18, Iss 2, p e

    2023  Volume 0281371

    Abstract: Objective There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize ... ...

    Abstract Objective There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAAs in order to identify novel biomarkers of disease. Methods Patients undergoing duplex ultrasound (US) or computed tomography (CT) for screening or surveillance of an AAA were screened to participate in the study. Cases with AAA were defined as having a max aortic diameter >3 cm. Circulating plasma exosomes were isolated using Cushioned-Density Gradient Ultracentrifugation and total RNA was extracted. Next Generation Sequencing was performed on the Illumina HiSeq4000 SE50. Differential miRNA expression analysis was performed using DESeq2 software with a Benjamini-Hochberg correction. MicroRNA expression profiles were validated by Quantitative Real-Time PCR. Results A total of 109 patients were screened to participate in the study. Eleven patients with AAA and 15 non-aneurysmal controls met study criteria and were enrolled. Ultrasound measured aortic diameter was significantly larger in the AAA group (mean maximum diameter 4.3 vs 2.0 cm, P = 6.45x10-6). More AAA patients had coronary artery disease (5/11 vs 1/15, P = 0.05) as compared to controls, but the groups did not differ significantly in the rates of peripheral arterial disease and chronic obstructive pulmonary disease. A total of 40 miRNAs were differentially expressed (P<0.05). Of these, 18 miRNAs were downregulated and 22 were upregulated in the AAA group compared to controls. After false discovery rate (FDR) adjustment, only miR-122-5p was expressed at significantly different levels in the AAA group compared to controls (fold change = 5.03 controls vs AAA; raw P = 1.8x10-5; FDR P = 0.02). Conclusion Plasma exosomes from AAA patients have significantly reduced levels of miRNA-122-5p compared to controls. This is a novel exosome-associated ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Molecular programs of fibrotic change in aging human lung

    Seoyeon Lee / Mohammad Naimul Islam / Kaveh Boostanpour / Dvir Aran / Guangchun Jin / Stephanie Christenson / Michael A. Matthay / Walter L. Eckalbar / Daryle J. DePianto / Joseph R. Arron / Liam Magee / Sunita Bhattacharya / Rei Matsumoto / Masaru Kubota / Donna L. Farber / Jahar Bhattacharya / Paul J. Wolters / Mallar Bhattacharya

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired ... ...

    Abstract Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired alveolar function in the natural history of human lung aging.
    Keywords Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms.

    Elizabeth D Hutchins / Glenn J Markov / Walter L Eckalbar / Rajani M George / Jesse M King / Minami A Tokuyama / Lauren A Geiger / Nataliya Emmert / Michael J Ammar / April N Allen / Ashley L Siniard / Jason J Corneveaux / Rebecca E Fisher / Juli Wade / Dale F DeNardo / J Alan Rawls / Matthew J Huentelman / Jeanne Wilson-Rawls / Kenro Kusumi

    PLoS ONE, Vol 9, Iss 8, p e

    2014  Volume 105004

    Abstract: Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first ... ...

    Abstract Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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