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  1. Article: Old-growth Douglas-fir forests

    Barrows, K

    Fremontia. Jan 1984. v. 11 (4)

    1984  

    Title variant Old-growth Douglas-fir forests [Pseudotsuga menziesii, ecology, vegetation, California]
    Keywords forests ; Pseudotsuga menziesii ; ecology ; vegetation ; California
    Language English
    Dates of publication 1984-01
    Size p. 20-23., ill.
    Document type Article
    Database NAL-Catalogue (AGRICOLA)

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  2. Article: MED1 IDR acetylation reorganizes the transcription preinitiation complex, rewires 3D chromatin interactions and reprograms gene expression.

    Lin, Ran / Barrows, Douglas / Mo, Yan / Onikubo, Takashi / Zhang, Zhiguo / Roeder, Robert G

    bioRxiv : the preprint server for biology

    2024  

    Abstract: With our current appreciation of the complexity of eukaryotic transcription, whose dysregulation drives diseases including cancer, it is becoming apparent that identification of key events coordinating multiple aspects of transcriptional regulation is of ...

    Abstract With our current appreciation of the complexity of eukaryotic transcription, whose dysregulation drives diseases including cancer, it is becoming apparent that identification of key events coordinating multiple aspects of transcriptional regulation is of special importance. To elucidate how assembly of RNA polymerase II (Pol II) with Mediator complex preinitiation complexes (PICs) and formation of transcription-permissive 3D chromatin organization are coordinated, we studied MED1, a representative subunit of the Mediator complex that acts to establish functional preinitiation complexes (PICs) that forms biomolecular condensates through an intrinsically disordered region (IDR) to facilitate transcription, and is implicated in the function of estrogen receptor α (hereafter ER) in ER-positive breast cancer (ER+ BC) cells. We found that MED1 is acetylated at 6 lysines in its IDR and, further, that MCF7 ER+ BC cells in which endogenous MED1 is replaced by an ectopic 6KR (non-acetylatable) mutant (6KR cells) exhibit enhanced cell growth and elevated expression of MED1-dependent genes. These results indicate an enhanced function of 6KR MED1 that may be attributed to two mechanisms: (1) reorganized PIC assembly, as indicated by increased MED1 and Pol II, decreased MED17, and equivalent ERα occupancies on chromatin, particularly at active enhancers and promoters; (2) sub-TAD chromatin unfolding, as revealed by HiCAR (Hi-C on accessible regulatory DNA) analyses. Furthermore, in vitro assays demonstrate distinct physio-chemical properties of liquid-liquid phase separation (LLPS) for 6KR versus 6KQ MED1 IDRs, and for non-acetylated versus CBP-acetylated WT MED1 IDR fragments. Related, Pol II CTD heptads are sequestered in 6KR and control WT MED1 IDR condensates, but not 6KQ and CBP-acetylated WT MED1 IDR condensates. These findings, in conjunction with recent reports of PIC structures, indicate that MED1 coordinates reorganization of the PIC machinery and the rewiring of regional chromatin organization through acetylation of its IDR. This study leads to an understanding of how the transition in phase behavior of a transcription cofactor acts as a mechanistic hub integrating linear and spatial chromatin functions to support gene expression, and have potential therapeutic implications for diseases involving MED1/Mediator-mediated transcription control.
    Language English
    Publishing date 2024-03-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.18.585606
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: ATRX guards against aberrant differentiation in mesenchymal progenitor cells.

    Fang, Yan / Barrows, Douglas / Dabas, Yakshi / Carroll, Thomas S / Tap, William D / Nacev, Benjamin A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Alterations in the tumor ... ...

    Abstract Alterations in the tumor suppressor
    Language English
    Publishing date 2023-08-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.08.552433
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ATRX guards against aberrant differentiation in mesenchymal progenitor cells.

    Fang, Yan / Barrows, Douglas / Dabas, Yakshi / Carroll, Thomas S / Singer, Sam / Tap, William D / Nacev, Benjamin A

    Nucleic acids research

    2024  

    Abstract: Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin ... ...

    Abstract Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks. We additionally observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Finally, we demonstrated that loss of ATRX in a mesenchymal malignancy, undifferentiated pleomorphic sarcoma, results in similar epigenetic disruption and de-repression of transposable elements. Together, our results reveal a role for ATRX in maintaining epigenetic states and transcriptional repression in mesenchymal progenitors and tumor cells and in preventing aberrant differentiation in the progenitor context.
    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkae160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.

    Bielopolski, Dana / Musante, Luca / Hoorn, Ewout J / Molina, Henrik / Barrows, Douglas / Carroll, Thomas / Harding, Michael A / Upson, Samantha / Qureshi, Adam / Weder, Max M / Tobin, Jonathan N / Kost, Rhonda G / Erdbrügger, U

    American journal of physiology. Renal physiology

    2024  

    Abstract: The Dietary Approach to Stop Hypertension (DASH) diet, with its low sodium and high potassium content, acts like a diuretic by reducing sodium reabsorption in the kidney's distal convoluted tubule but without the side effects. Previous studies based on ... ...

    Abstract The Dietary Approach to Stop Hypertension (DASH) diet, with its low sodium and high potassium content, acts like a diuretic by reducing sodium reabsorption in the kidney's distal convoluted tubule but without the side effects. Previous studies based on animal models didn't explore changes in human ion channel proteins. Recent insights into urinary extracellular vesicles (uEVs) suggest they reflect kidney tissue and physiological modifications. In our inpatient study, we shifted hypertensive volunteers from an American diet to the DASH diet, examining changes in those with stage 1 untreated hypertension. We analyzed a large range of pure uEVs, from small to large, in urine samples from nine volunteers over three time points. Mass spectrometry of these uEVs identified 1,800 proteins, revealing an increase in SCL12A3 (NCC) and a decrease in aquaporin 2 (AQP2). Immunoblotting showed an increase in activated (phosphorylated) NCC ratio to total NCC and a decrease in AQP2 from day 5 to 11, indicating the DASH diet induces measurable kidney responses via uEV protein abundance changes. This non-invasive method offers new insights into the diet's renal mechanism. Future studies should confirm these findings in a larger cohort, clarify the drivers behind NCC and AQP2 changes, their impact on hypertension, and investigate if uEVs also act as a waste pathway for inactive proteins, expanding our understanding of dietary effects on kidney physiology.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00274.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Integration of energy systems.

    Arent, Douglas J / Barrows, Clayton / Davis, Steven / Grim, Gary / Schaidle, Joshua / Kroposki, Ben / Ruth, Mark / Van Zandt, Brooke

    MRS bulletin

    2022  Volume 46, Issue 12, Page(s) 1139–1152

    Language English
    Publishing date 2022-01-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2136359-6
    ISSN 1938-1425 ; 0883-7694
    ISSN (online) 1938-1425
    ISSN 0883-7694
    DOI 10.1557/s43577-021-00244-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Loss of UTX/KDM6A and the activation of FGFR3 converge to regulate differentiation gene-expression programs in bladder cancer.

    Barrows, Douglas / Feng, Lijuan / Carroll, Thomas S / Allis, C David

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 41, Page(s) 25732–25741

    Abstract: Bladder cancer prognosis is closely linked to the underlying differentiation state of the tumor, ranging from the less aggressive and most-differentiated luminal tumors to the more aggressive and least-differentiated basal tumors. Sequencing of bladder ... ...

    Abstract Bladder cancer prognosis is closely linked to the underlying differentiation state of the tumor, ranging from the less aggressive and most-differentiated luminal tumors to the more aggressive and least-differentiated basal tumors. Sequencing of bladder cancer has revealed that loss-of-function mutations in chromatin regulators and mutations that activate receptor tyrosine kinase (RTK) signaling frequently occur in bladder cancer. However, little is known as to whether and how these two types of mutations functionally interact or cooperate to regulate tumor growth and differentiation state. Here, we focus on loss of the histone demethylase UTX (also known as KDM6A) and activation of the RTK FGFR3, two events that commonly cooccur in muscle invasive bladder tumors. We show that UTX loss and FGFR3 activation cooperate to disrupt the balance of luminal and basal gene expression in bladder cells. UTX localized to enhancers surrounding many genes that are important for luminal cell fate, and supported the transcription of these genes in a catalytic-independent manner. In contrast to UTX, FGFR3 activation was associated with lower expression of luminal genes in tumors and FGFR inhibition increased transcription of these same genes in cell culture models. This suggests an antagonistic relationship between UTX and FGFR3. In support of this model, UTX loss-of-function potentiated FGFR3-dependent transcriptional effects and the presence of UTX blocked an FGFR3-mediated increase in the colony formation of bladder cells. Taken together, our study reveals how mutations in UTX and FGFR3 converge to disrupt bladder differentiation programs that could serve as a therapeutic target.
    MeSH term(s) Cell Differentiation ; Chromatin/genetics ; Chromatin/metabolism ; Cohort Studies ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Histone Demethylases/metabolism ; Humans ; Mutation ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/metabolism ; Urinary Bladder Neoplasms/physiopathology
    Chemical Substances Chromatin ; Histone Demethylases (EC 1.14.11.-) ; KDM6A protein, human (EC 1.14.11.-) ; FGFR3 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
    Language English
    Publishing date 2020-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2008017117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A Huge 2015 Butterfly Feeding Aggregation in Northeastern Kansas, U.S.A., with Comparative Notes (Lepidoptera: Lycaenidae, Nymphalidae, Pieridae)

    Barrows, Edward M

    Journal of the Kansas Entomological Society. 2019 Apr. 9, v. 91, no. 2

    2019  

    Abstract: ... species, dominated by Asterocampa celtis (northern-race Hackberry Emperor), occurred in Douglas and ...

    Abstract In June 2015, a huge, adult butterfly feeding aggregation of thousands of individuals in seven species, dominated by Asterocampa celtis (northern-race Hackberry Emperor), occurred in Douglas and Jefferson Counties, Kansas. This aggregation differed in species composition from smaller aggregations in the same observation area in 1970–1971. A rare A. celtis melanic form was in both the 1970 and 2015 aggregations. Vehicles killed thousands of butterflies in the 2015 aggregation. This study also summarizes data on local population sizes of A. celtis and Asterocampa clyton (Tawny Emperor) in the U.S. and provides new adult food records obtained from eight of the butterfly species in the aggregations.
    Keywords adults ; butterflies ; Celtis ; food records ; Lycaenidae ; Nymphalidae ; Pieridae ; population size ; species diversity ; Kansas
    Language English
    Dates of publication 2019-0409
    Size p. 133-143.
    Publishing place Kansas Entomological Society
    Document type Article
    ZDB-ID 2210268-1
    ISSN 0022-8567
    ISSN 0022-8567
    DOI 10.2317/0022-8567-91.2.133
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Altered chromatin occupancy of patient-associated H4 mutants misregulate neuronal differentiation.

    Feng, Lijuan / Barrows, Douglas / Zhong, Liangwen / Mätlik, Kärt / Porter, Elizabeth G / Djomo, Annaelle M / Yau, Iris / Soshnev, Alexey A / Carroll, Thomas S / Wen, Duancheng / Hatten, Mary E / Garcia, Benjamin A / Allis, C David

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Chromatin is a crucial regulator of gene expression and tightly controls development across species. Mutations in only one copy of multiple histone genes were identified in children with developmental disorders characterized by microcephaly, but their ... ...

    Abstract Chromatin is a crucial regulator of gene expression and tightly controls development across species. Mutations in only one copy of multiple histone genes were identified in children with developmental disorders characterized by microcephaly, but their mechanistic roles in development remain unclear. Here we focus on dominant mutations affecting histone H4 lysine 91. These H4K91 mutants form aberrant nuclear puncta at specific heterochromatin regions. Mechanistically, H4K91 mutants demonstrate enhanced binding to the histone variant H3.3, and ablation of H3.3 or the H3.3-specific chaperone DAXX diminishes the mutant localization to chromatin. Our functional studies demonstrate that H4K91 mutant expression increases chromatin accessibility, alters developmental gene expression through accelerating pro-neural differentiation, and causes reduced mouse brain size
    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.29.560141
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Mitophagy restricts BAX/BAK-independent, Parkin-mediated apoptosis.

    Quarato, Giovanni / Mari, Luigi / Barrows, Nicholas J / Yang, Mao / Ruehl, Sebastian / Chen, Mark J / Guy, Cliff S / Low, Jonathan / Chen, Taosheng / Green, Douglas R

    Science advances

    2023  Volume 9, Issue 21, Page(s) eadg8156

    Abstract: Degradation of defective mitochondria is an essential process to maintain cellular homeostasis and it is strictly regulated by the ubiquitin-proteasome system (UPS) and lysosomal activities. Here, using genome-wide CRISPR and small interference RNA ... ...

    Abstract Degradation of defective mitochondria is an essential process to maintain cellular homeostasis and it is strictly regulated by the ubiquitin-proteasome system (UPS) and lysosomal activities. Here, using genome-wide CRISPR and small interference RNA screens, we identified a critical contribution of the lysosomal system in controlling aberrant induction of apoptosis following mitochondrial damage. After treatment with mitochondrial toxins, activation of the PINK1-Parkin axis triggered a BAX- and BAK-independent process of cytochrome c release from mitochondria followed by APAF1 and caspase 9-dependent apoptosis. This phenomenon was mediated by UPS-dependent outer mitochondrial membrane (OMM) degradation and was reversed using proteasome inhibitors. We found that the subsequent recruitment of the autophagy machinery to the OMM protected cells from apoptosis, mediating the lysosomal degradation of dysfunctional mitochondria. Our results underscore a major role of the autophagy machinery in counteracting aberrant noncanonical apoptosis and identified autophagy receptors as key elements in the regulation of this process.
    MeSH term(s) Mitophagy ; bcl-2-Associated X Protein/genetics ; Apoptosis ; Autophagy ; Mitochondria ; Ubiquitin
    Chemical Substances bcl-2-Associated X Protein ; Ubiquitin
    Language English
    Publishing date 2023-05-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adg8156
    Database MEDical Literature Analysis and Retrieval System OnLINE

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