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  1. Article: The neurological toxicity of heavy metals: A fish perspective

    Green, Adrian J / Planchart, Antonio

    Comparative biochemistry and physiology. 2018 June, v. 208

    2018  

    Abstract: The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played ...

    Abstract The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research.
    Keywords Danio rerio ; brain ; cadmium ; environmental exposure ; fish ; genetically modified organisms ; heavy metals ; lead ; mercury ; models ; morbidity ; neurodegenerative diseases ; neurons ; toxicity
    Language English
    Dates of publication 2018-06
    Size p. 12-19.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 189285-x
    ISSN 0306-4492 ; 0742-8413 ; 1532-0456
    ISSN 0306-4492 ; 0742-8413 ; 1532-0456
    DOI 10.1016/j.cbpc.2017.11.008
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 71/715: Show issues

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  2. Article: Deep autoencoder-based behavioral pattern recognition outperforms standard statistical methods in high-dimensional zebrafish studies.

    Green, Adrian J / Truong, Lisa / Thunga, Preethi / Leong, Connor / Hancock, Melody / Tanguay, Robyn L / Reif, David M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Zebrafish have become an essential tool in screening for developmental neurotoxic chemicals and their molecular targets. The success of zebrafish as a screening model is partially due to their physical characteristics including their relatively simple ... ...

    Abstract Zebrafish have become an essential tool in screening for developmental neurotoxic chemicals and their molecular targets. The success of zebrafish as a screening model is partially due to their physical characteristics including their relatively simple nervous system, rapid development, experimental tractability, and genetic diversity combined with technical advantages that allow for the generation of large amounts of high-dimensional behavioral data. These data are complex and require advanced machine learning and statistical techniques to comprehensively analyze and capture spatiotemporal responses. To accomplish this goal, we have trained semi-supervised deep autoencoders using behavior data from unexposed larval zebrafish to extract quintessential "normal" behavior. Following training, our network was evaluated using data from larvae shown to have significant changes in behavior (using a traditional statistical framework) following exposure to toxicants that include nanomaterials, aromatics, per- and polyfluoroalkyl substances (PFAS), and other environmental contaminants. Further, our model identified new chemicals (Perfluoro-n-octadecanoic acid, 8-Chloroperfluorooctylphosphonic acid, and Nonafluoropentanamide) as capable of inducing abnormal behavior at multiple chemical-concentrations pairs not captured using distance moved alone. Leveraging this deep learning model will allow for better characterization of the different exposure-induced behavioral phenotypes, facilitate improved genetic and neurobehavioral analysis in mechanistic determination studies and provide a robust framework for analyzing complex behaviors found in higher-order model systems.
    Language English
    Publishing date 2023-09-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.13.557544
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  3. Article ; Online: Developmental cadmium exposure disrupts zebrafish vestibular calcium channels interfering with otolith formation and inner ear function.

    Green, Adrian J / Wall, Alex R / Weeks, Ryan D / Mattingly, Carolyn J / Marsden, Kurt C / Planchart, Antonio

    Neurotoxicology

    2023  Volume 96, Page(s) 129–139

    Abstract: Dizziness or balance problems are estimated to affect approximately 3.3 million children aged three to 17 years. These disorders develop from a breakdown in the balance control system and can be caused by anything that affects the inner ear or the brain, ...

    Abstract Dizziness or balance problems are estimated to affect approximately 3.3 million children aged three to 17 years. These disorders develop from a breakdown in the balance control system and can be caused by anything that affects the inner ear or the brain, including exposure to environmental toxicants. One potential environmental toxicant linked to balance disorders is cadmium, an extremely toxic metal that occurs naturally in the earth's crust and is released as a byproduct of industrial processes. Cadmium is associated with balance and vestibular dysfunction in adults exposed occupationally, but little is known about the developmental effects of low-concentration cadmium exposure. Our findings indicate that zebrafish exposed to 10-60 parts per billion (ppb) cadmium from four hours post-fertilization (hpf) to seven days post-fertilization (dpf) exhibit abnormal behaviors, including pronounced increases in auditory sensitivity and circling behavior, both of which are linked to reductions in otolith growth and are rescued by the addition of calcium to the media. Pharmacological intervention shows that agonist-induced activation of the P2X calcium ion channel in the presence of cadmium restores otolith size. In conclusion, cadmium-induced ototoxicity is linked to vestibular-based behavioral abnormalities and auditory sensitivity following developmental exposure, and calcium ion channel function is associated with these defects.
    MeSH term(s) Animals ; Zebrafish ; Cadmium/toxicity ; Otolithic Membrane ; Vestibule, Labyrinth ; Vestibular Diseases
    Chemical Substances Cadmium (00BH33GNGH)
    Language English
    Publishing date 2023-04-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 800820-6
    ISSN 1872-9711 ; 0161-813X
    ISSN (online) 1872-9711
    ISSN 0161-813X
    DOI 10.1016/j.neuro.2023.04.006
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1547: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD

    Weeks, Ryan D / Banack, Sandra A / Howell, Shaunacee / Thunga, Preethi / Metcalf, James S / Green, Adrian J / Cox, Paul A / Planchart, Antonio

    Neurotoxicity research

    2023  Volume 41, Issue 5, Page(s) 481–495

    Abstract: β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA ... ...

    Abstract β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.
    MeSH term(s) Animals ; Zebrafish ; Neurodegenerative Diseases/etiology ; Amyotrophic Lateral Sclerosis/chemically induced ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/complications ; Amino Acids, Diamino/toxicity ; Animals, Genetically Modified ; Neurotoxins/toxicity ; Superoxide Dismutase
    Chemical Substances beta-N-methylamino-L-alanine (108SA6URTV) ; Amino Acids, Diamino ; Neurotoxins ; Superoxide Dismutase (EC 1.15.1.1)
    Language English
    Publishing date 2023-08-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2036826-4
    ISSN 1476-3524 ; 1029-8428
    ISSN (online) 1476-3524
    ISSN 1029-8428
    DOI 10.1007/s12640-023-00658-z
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5749: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Correction to: The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD

    Weeks, Ryan D / Banack, Sandra A / Howell, Shaunacee / Thunga, Preethi / Metcalf, James S / Green, Adrian J / Cox, Paul A / Planchart, Antonio

    Neurotoxicity research

    2023  Volume 41, Issue 5, Page(s) 496

    Language English
    Publishing date 2023-08-24
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2036826-4
    ISSN 1476-3524 ; 1029-8428
    ISSN (online) 1476-3524
    ISSN 1029-8428
    DOI 10.1007/s12640-023-00664-1
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5749: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: The neurological toxicity of heavy metals: A fish perspective.

    Green, Adrian J / Planchart, Antonio

    Comparative biochemistry and physiology. Toxicology & pharmacology : CBP

    2017  Volume 208, Page(s) 12–19

    Abstract: The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played ...

    Abstract The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Behavior, Animal/drug effects ; Disease Models, Animal ; Gene Expression Regulation, Developmental/drug effects ; Heavy Metal Poisoning, Nervous System/etiology ; Heavy Metal Poisoning, Nervous System/genetics ; Heavy Metal Poisoning, Nervous System/metabolism ; Heavy Metal Poisoning, Nervous System/pathology ; Humans ; Metals, Heavy/toxicity ; Nerve Degeneration ; Nervous System/drug effects ; Nervous System/metabolism ; Nervous System/pathology ; Nervous System/physiopathology ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Risk Assessment ; Water Pollutants, Chemical/toxicity ; Zebrafish/genetics ; Zebrafish/metabolism
    Chemical Substances Metals, Heavy ; Water Pollutants, Chemical
    Language English
    Publishing date 2017-12-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 189285-x
    ISSN 1532-0456 ; 0306-4492 ; 0742-8413
    ISSN 1532-0456 ; 0306-4492 ; 0742-8413
    DOI 10.1016/j.cbpc.2017.11.008
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 44/C: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.

    Green, Adrian J / Anchang, Benedict / Akhtari, Farida S / Reif, David M / Motsinger-Reif, Alison

    Pharmacogenomics

    2021  Volume 22, Issue 9, Page(s) 543–551

    Abstract: Combination drug therapies have become an integral part of precision oncology, and while evidence of clinical effectiveness continues to grow, the underlying mechanisms supporting synergy are poorly understood. Immortalized human lymphoblastoid cell ... ...

    Abstract Combination drug therapies have become an integral part of precision oncology, and while evidence of clinical effectiveness continues to grow, the underlying mechanisms supporting synergy are poorly understood. Immortalized human lymphoblastoid cell lines (LCLs) have been proven as a particularly useful, scalable and low-cost model in pharmacogenetics research, and are suitable for elucidating the molecular mechanisms of synergistic combination therapies. In this review, we cover the advantages of LCLs in synergy pharmacogenomics and consider recent studies providing initial evidence of the utility of LCLs in synergy research. We also discuss several opportunities for LCL-based systems to address gaps in the research through the expansion of testing regimens, assessment of new drug classes and higher-order combinations, and utilization of integrated omics technologies.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cell Line, Tumor/drug effects ; Humans ; Lymphocytes/drug effects ; Pharmacogenomic Testing/methods
    Language English
    Publishing date 2021-05-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 2019513-8
    ISSN 1744-8042 ; 1462-2416
    ISSN (online) 1744-8042
    ISSN 1462-2416
    DOI 10.2217/pgs-2020-0160
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5247: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article: RYK

    Gonzalez, Ricardo D / Small, George W / Green, Adrian J / Akhtari, Farida S / Havener, Tammy M / Quintanilha, Julia C F / Cipriani, Amber B / Reif, David M / McLeod, Howard L / Motsinger-Reif, Alison A / Wiltshire, Tim

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 5

    Abstract: Temozolomide (TMZ) chemotherapy is an important tool in the treatment of glioma brain tumors. However, variable patient response and chemo-resistance remain exceptionally challenging. Our previous genome-wide association study (GWAS) identified a ... ...

    Abstract Temozolomide (TMZ) chemotherapy is an important tool in the treatment of glioma brain tumors. However, variable patient response and chemo-resistance remain exceptionally challenging. Our previous genome-wide association study (GWAS) identified a suggestively significant association of SNP rs4470517 in the
    Language English
    Publishing date 2023-05-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16050726
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  9. Article: MKX-AS1

    Gonzalez, Ricardo D / Small, George W / Green, Adrian J / Akhtari, Farida S / Motsinger-Reif, Alison A / Quintanilha, Julia C F / Havener, Tammy M / Reif, David M / McLeod, Howard L / Wiltshire, Tim

    Pharmaceuticals (Basel, Switzerland)

    2023  Volume 16, Issue 5

    Abstract: Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA ... ...

    Abstract Oxaliplatin (OXAL) is a commonly used chemotherapy for treating colorectal cancer (CRC). A recent genome wide association study (GWAS) showed that a genetic variant (rs11006706) in the lncRNA gene
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph16050757
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pharmacogenomic Analyses Implicate B Cell Developmental Status and

    Small, George W / Akhtari, Farida S / Green, Adrian J / Havener, Tammy M / Sikes, Michael / Quintanhila, Julia / Gonzalez, Ricardo D / Reif, David M / Motsinger-Reif, Alison A / McLeod, Howard L / Wiltshire, Tim

    Cells

    2023  Volume 12, Issue 12

    Abstract: Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may ... ...

    Abstract Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene
    MeSH term(s) Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal/genetics ; Antigens, CD20/genetics ; Antineoplastic Agents ; Pharmacogenomic Testing ; Prednisolone ; Humans
    Chemical Substances Antibodies, Monoclonal ; Antigens, CD20 ; Antineoplastic Agents ; Prednisolone (9PHQ9Y1OLM)
    Language English
    Publishing date 2023-06-07
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12121574
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