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  1. Article: Genomically anchored vitamin D receptor mediates an abundance of bioprotective actions elicited by its 1,25-dihydroxyvitamin D hormonal ligand.

    Haussler, Mark R / Haussler, Carol A / Jurutka, Peter W

    Vitamins and hormones

    2023  Volume 123, Page(s) 313–383

    Abstract: The nuclear vitamin D receptor (VDR) mediates the actions of its physiologic 1,25-dihydroxyvitamin ... ...

    Abstract The nuclear vitamin D receptor (VDR) mediates the actions of its physiologic 1,25-dihydroxyvitamin D
    MeSH term(s) Humans ; Calcium ; Ligands ; Parathyroid Hormone ; Receptors, Calcitriol/genetics
    Chemical Substances 1,25-dihydroxyvitamin D (66772-14-3) ; Calcium (SY7Q814VUP) ; Ligands ; Parathyroid Hormone ; Receptors, Calcitriol ; VDR protein, human
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 201161-x
    ISSN 2162-2620 ; 0083-6729
    ISSN (online) 2162-2620
    ISSN 0083-6729
    DOI 10.1016/bs.vh.2022.12.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Targeting Bacterial Gyrase with Cystobactamid, Fluoroquinolone, and Aminocoumarin Antibiotics Induces Distinct Molecular Signatures in Pseudomonas aeruginosa.

    Franke, Raimo / Overwin, Heike / Häussler, Susanne / Brönstrup, Mark

    mSystems

    2021  Volume 6, Issue 4, Page(s) e0061021

    Abstract: The design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to ... ...

    Abstract The design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to different sites of the same target can be differentiated by their transcriptome or metabolome signatures. The effects of three fluoroquinolones, two aminocoumarins, and two cystobactamids, all inhibiting bacterial gyrase, on Pseudomonas aeruginosa at subinhibitory concentrations could be distinguished clearly by RNA sequencing as well as metabolomics. We observed a strong (2.8- to 212-fold) induction of autolysis-triggering pyocins in all gyrase inhibitors, which correlated with extracellular DNA (eDNA) release. Gyrase B-binding aminocoumarins induced the most pronounced changes, including a strong downregulation of phenazine and rhamnolipid virulence factors. Cystobactamids led to a downregulation of a glucose catabolism pathway. The study implies that clustering cellular mechanisms of action according to the primary target needs to take class-dependent variances into account.
    Language English
    Publishing date 2021-07-13
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.00610-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Vitamin D Receptor Mediates a Myriad of Biological Actions Dependent on Its 1,25-Dihydroxyvitamin D Ligand: Distinct Regulatory Themes Revealed by Induction of Klotho and Fibroblast Growth Factor-23.

    Haussler, Mark R / Livingston, Sarah / Sabir, Zhela L / Haussler, Carol A / Jurutka, Peter W

    JBMR plus

    2020  Volume 5, Issue 1, Page(s) e10432

    Abstract: The hormonal vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH) ...

    Abstract The hormonal vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH)
    Language English
    Publishing date 2020-12-03
    Publishing country England
    Document type Journal Article
    ISSN 2473-4039
    ISSN (online) 2473-4039
    DOI 10.1002/jbm4.10432
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  4. Article ; Online: Targeting Bacterial Gyrase with Cystobactamid, Fluoroquinolone, and Aminocoumarin Antibiotics Induces Distinct Molecular Signatures in Pseudomonas aeruginosa.

    Franke, Raimo / Overwin, Heike / Häussler, Susanne / Brönstrup, Mark

    e0061021 ; mSystems ; United States

    2021  

    Abstract: The design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to ... ...

    Abstract The design of novel antibiotics relies on a profound understanding of their mechanism of action. While it has been shown that cellular effects of antibiotics cluster according to their molecular targets, we investigated whether compounds binding to different sites of the same target can be differentiated by their transcriptome or metabolome signatures. The effects of three fluoroquinolones, two aminocoumarins, and two cystobactamids, all inhibiting bacterial gyrase, on Pseudomonas aeruginosa at subinhibitory concentrations could be distinguished clearly by RNA sequencing as well as metabolomics. We observed a strong (2.8- to 212-fold) induction of autolysis-triggering pyocins in all gyrase inhibitors, which correlated with extracellular DNA (eDNA) release. Gyrase B-binding aminocoumarins induced the most pronounced changes, including a strong downregulation of phenazine and rhamnolipid virulence factors. Cystobactamids led to a downregulation of a glucose catabolism pathway. The study implies that clustering cellular mechanisms of action according to the primary target needs to take class-dependent variances into account. IMPORTANCE Novel antibiotics are urgently needed to tackle the growing worldwide problem of antimicrobial resistance. Bacterial pathogens possess few privileged targets for a successful therapy: the majority of existing antibiotics as well as current candidates in development target the complex bacterial machinery for cell wall synthesis, protein synthesis, or DNA replication. An important mechanistic question addressed by this study is whether inhibiting such a complex target at different sites with different compounds has similar or differentiated cellular consequences. Using transcriptomics and metabolomics, we demonstrate that three different classes of gyrase inhibitors can be distinguished by their molecular signatures in P. aeruginosa. We describe the cellular effects of a promising, recently identified gyrase inhibitor class, the cystobactamids, in comparison to those of the established gyrase A-binding fluoroquinolones and the gyrase B-binding aminocoumarins. The study results have implications for mode-of-action discovery approaches based on target-specific reference compounds, as they highlight the intraclass variability of cellular compound effects.
    Keywords DNA gyrase ; Pseudomonas aeruginosa ; RNA sequencing ; antibiotics ; gyrase ; metabolomics ; mode of action
    Subject code 500
    Language English
    Publishing date 2021-07-13
    Publisher ASM
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Pomegranate derivative urolithin A enhances vitamin D receptor signaling to amplify serotonin-related gene induction by 1,25-dihydroxyvitamin D.

    Livingston, Sarah / Mallick, Sanchita / Lucas, Daniel A / Sabir, Marya S / Sabir, Zhela L / Purdin, Hespera / Nidamanuri, Sree / Haussler, Carol A / Haussler, Mark R / Jurutka, Peter W

    Biochemistry and biophysics reports

    2020  Volume 24, Page(s) 100825

    Abstract: Mediated by the nuclear vitamin D receptor (VDR), the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin ... ...

    Abstract Mediated by the nuclear vitamin D receptor (VDR), the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D
    Language English
    Publishing date 2020-10-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2831046-9
    ISSN 2405-5808 ; 2405-5808
    ISSN (online) 2405-5808
    ISSN 2405-5808
    DOI 10.1016/j.bbrep.2020.100825
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Optimal vitamin D spurs serotonin: 1,25-dihydroxyvitamin D represses serotonin reuptake transport (

    Sabir, Marya S / Haussler, Mark R / Mallick, Sanchita / Kaneko, Ichiro / Lucas, Daniel A / Haussler, Carol A / Whitfield, G Kerr / Jurutka, Peter W

    Genes & nutrition

    2018  Volume 13, Page(s) 19

    Abstract: Background: Diminished brain levels of two neurohormones, 5-hydroxytryptamine (5-HT; serotonin) and 1,25-dihydroxyvitamin D: Results: Employing quantitative real-time PCR, we demonstrate that : Conclusions: These results are consistent with the ... ...

    Abstract Background: Diminished brain levels of two neurohormones, 5-hydroxytryptamine (5-HT; serotonin) and 1,25-dihydroxyvitamin D
    Results: Employing quantitative real-time PCR, we demonstrate that
    Conclusions: These results are consistent with the concept that vitamin D maintains extracellular fluid serotonin concentrations in the brain, thereby offering an explanation for how vitamin D could influence the trajectory and development of neuropsychiatric disorders. Given the profile of gene regulation in cultured RN46A-B14 serotonergic neurons, we conclude that 1,25D acts not only to induce serotonin synthesis, but also functions at an indirect, molecular-genomic stage to mimic SSRIs and MAO inhibitors, likely elevating serotonin in the CNS. These data suggest that optimal vitamin D status may contribute to improving behavioral pathophysiologies resulting from dysregulation of serotonergic neurotransmission.
    Language English
    Publishing date 2018-07-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2416599-2
    ISSN 1865-3499 ; 1555-8932
    ISSN (online) 1865-3499
    ISSN 1555-8932
    DOI 10.1186/s12263-018-0605-7
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    In stock of ZB MED Bonn / Germany

    Z 7828: Show issues

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  7. Article: GenArk: Towards a million UCSC Genome Browsers.

    Clawson, Hiram / Lee, Brian T / Raney, Brian J / Barber, Galt P / Casper, Jonathan / Diekhans, Mark / Fischer, Clay / Gonzalez, Jairo Navarro / Hinrichs, Angie S / Lee, Christopher M / Nassar, Luis R / Perez, Gerardo / Wick, Brittney / Schmelter, Daniel / Speir, Matthew L / Armstrong, Joel / Zweig, Ann S / Kuhn, Robert M / Kirilenko, Bogdan M /
    Hiller, Michael / Haussler, David / Kent, W James / Haeussler, Maximilian

    Research square

    2023  

    Abstract: Interactive graphical genome browsers are essential tools for biologists working with DNA sequences. Although tens of thousands of new genome assemblies have become available over the last decade, accessibility is limited by the work involved in manually ...

    Abstract Interactive graphical genome browsers are essential tools for biologists working with DNA sequences. Although tens of thousands of new genome assemblies have become available over the last decade, accessibility is limited by the work involved in manually creating browsers and curating annotations. The results can push the limits of data storage infrastructure. To facilitate managing this increasing number of genome assemblies, we created the Genome Archive (GenArk) collection of UCSC Genome Browsers from assemblies hosted at NCBI(1). Built on our established assembly hub system, this collection enables fast, on-demand visualization of chromosome regions without requiring a database server. Available annotations include gene models, some mapped through whole-genome alignments, repeat masks, GC content, and others. We also modified our popular BLAT(2) aligner and in-silico PCR to support a large number of genomes using limited RAM. Users can upload additional annotations themselves via track hubs(3) and custom tracks. We can import more annotations in bulk from third-party resources, demonstrated here with TOGA(4) gene models. 2,430 GenArk assemblies are listed at https://hgdownload.soe.ucsc.edu/hubs/ and can be found by searching on the main UCSC gateway page. We will continue to add human high-quality assemblies and for other organisms, we are looking forward to receiving requests from the research community for ever more browsers and whole-genome alignments via http://genome.ucsc.edu/assemblyRequest.html.
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2697398/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: GenArk: towards a million UCSC genome browsers.

    Clawson, Hiram / Lee, Brian T / Raney, Brian J / Barber, Galt P / Casper, Jonathan / Diekhans, Mark / Fischer, Clay / Gonzalez, Jairo Navarro / Hinrichs, Angie S / Lee, Christopher M / Nassar, Luis R / Perez, Gerardo / Wick, Brittney / Schmelter, Daniel / Speir, Matthew L / Armstrong, Joel / Zweig, Ann S / Kuhn, Robert M / Kirilenko, Bogdan M /
    Hiller, Michael / Haussler, David / Kent, W James / Haeussler, Maximilian

    Genome biology

    2023  Volume 24, Issue 1, Page(s) 217

    Abstract: Interactive graphical genome browsers are essential tools in genomics, but they do not contain all the recent genome assemblies. We create Genome Archive (GenArk) collection of UCSC Genome Browsers from NCBI assemblies. Built on our established track hub ...

    Abstract Interactive graphical genome browsers are essential tools in genomics, but they do not contain all the recent genome assemblies. We create Genome Archive (GenArk) collection of UCSC Genome Browsers from NCBI assemblies. Built on our established track hub system, this enables fast visualization of annotations. Assemblies come with gene models, repeat masks, BLAT, and in silico PCR. Users can add annotations via track hubs and custom tracks. We can bulk-import third-party resources, demonstrated with TOGA and Ensembl gene models for hundreds of assemblies.Three thousand two hundred sixty-nine GenArk assemblies are listed at https://hgdownload.soe.ucsc.edu/hubs/ and can be searched for on the Genome Browser gateway page.
    MeSH term(s) Software ; Genome ; Genomics ; Archives ; Nucleic Acid Amplification Techniques ; Databases, Genetic ; Internet
    Language English
    Publishing date 2023-10-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-03057-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Introduction: Special Issue on Vitamin D Dedicated to the Memory of Anthony W Norman.

    Bouillon, Roger / Haussler, Mark / Bikle, Dan / Christakos, Sylvia / Welsh, JoEllen

    JBMR plus

    2020  Volume 5, Issue 1, Page(s) e10445

    Language English
    Publishing date 2020-12-21
    Publishing country England
    Document type Editorial
    ISSN 2473-4039
    ISSN (online) 2473-4039
    DOI 10.1002/jbm4.10445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: 1,25-Dihydroxyvitamin D and Klotho: A Tale of Two Renal Hormones Coming of Age.

    Haussler, Mark R / Whitfield, G Kerr / Haussler, Carol A / Sabir, Marya S / Khan, Zainab / Sandoval, Ruby / Jurutka, Peter W

    Vitamins and hormones

    2016  Volume 100, Page(s) 165–230

    Abstract: 1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate ... ...

    Abstract 1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling exerts feedback control of Ca/PO4 via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, fibrosis, and associated pathologies. Vitamin D also elicits xenobiotic detoxification, oxidative stress reduction, neuroprotective functions, antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions, and cardiovascular benefits. Many of the healthspan advantages conferred by 1,25D are promulgated by its induction of klotho, a renal hormone that is an anti-aging enzyme/coreceptor that protects against skin atrophy, osteopenia, hyperphosphatemia, endothelial dysfunction, cognitive defects, neurodegenerative disorders, and impaired hearing. In addition to the high-affinity 1,25D hormone, low-affinity nutritional VDR ligands including curcumin, polyunsaturated fatty acids, and anthocyanidins initiate VDR signaling, whereas the longevity principles resveratrol and SIRT1 potentiate VDR signaling. 1,25D exerts actions against neural excitotoxicity and induces serotonin mood elevation to support cognitive function and prosocial behavior. Together, 1,25D and klotho maintain the molecular signaling systems that promote growth (p21), development (Wnt), antioxidation (Nrf2/FOXO), and homeostasis (FGF23) in tissues crucial for normal physiology, while simultaneously guarding against malignancy and degeneration. Therefore, liganded-VDR modulates the expression of a "fountain of youth" array of genes, with the klotho target emerging as a major player in the facilitation of health span by delaying the chronic diseases of aging.
    MeSH term(s) Animals ; Gene Expression Regulation/physiology ; Glucuronidase/genetics ; Glucuronidase/metabolism ; Humans ; Signal Transduction/physiology ; Vitamin D/analogs & derivatives ; Vitamin D/chemistry ; Vitamin D/pharmacology
    Chemical Substances Vitamin D (1406-16-2) ; 1,25-dihydroxyvitamin D (66772-14-3) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31)
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 201161-x
    ISSN 2162-2620 ; 0083-6729
    ISSN (online) 2162-2620
    ISSN 0083-6729
    DOI 10.1016/bs.vh.2015.11.005
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    In stock of ZB MED Cologne/Königswinter

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