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  1. Article: The ubiquitin-proteasome system in spongiform degenerative disorders.

    Whatley, Brandi R / Li, Lian / Chin, Lih-Shen

    Biochimica et biophysica acta

    2008  Volume 1782, Issue 12, Page(s) 700–712

    Abstract: Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from ...

    Abstract Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer's disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan's spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin-proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin-protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.
    MeSH term(s) Animals ; Humans ; Neurodegenerative Diseases/metabolism ; Prion Diseases/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism
    Chemical Substances Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Keywords covid19
    Language English
    Publishing date 2008-08-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbadis.2008.08.006
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  2. Article ; Online: Classics in Chemical Neuroscience: Pramipexole.

    Wilson, Sean M / Wurst, Madeline G / Whatley, Michael F / Daniels, R Nathan

    ACS chemical neuroscience

    2020  Volume 11, Issue 17, Page(s) 2506–2512

    Abstract: ... brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound ...

    Abstract Pramipexole was first manufactured by Pharmacia and Upjohn in July 1997 under the United States brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound that selectively agonizes the dopamine D
    MeSH term(s) Benzothiazoles ; Dopamine Agonists ; Humans ; Parkinson Disease/drug therapy ; Pramipexole ; Tremor
    Chemical Substances Benzothiazoles ; Dopamine Agonists ; Pramipexole (83619PEU5T)
    Language English
    Publishing date 2020-08-17
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.0c00332
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  3. Article ; Online: Interim report of the reactogenicity and immunogenicity of SARS-CoV-2 XBB-containing vaccines.

    Chalkias, Spyros / McGhee, Nichole / Whatley, Jordan L / Essink, Brandon / Brosz, Adam / Tomassini, Joanne E / Girard, Bethany / Edwards, Darin K / Wu, Kai / Nasir, Arshan / Lee, Diana / Avena, Laura E / Feng, Jing / Deng, Weiping / Montefiori, David C / Baden, Lindsey R / Miller, Jacqueline M / Das, Rituparna

    The Journal of infectious diseases

    2024  

    Abstract: Background: Monovalent Omicron XBB.1.5-containing vaccines were approved for Coronavirus disease 2019 (COVID-19) 2023-2024 immunizations.: Methods: This ongoing, open-label, phase 2/3 study evaluated mRNA-1273.815-monovalent (50-µg Omicron XBB.1.5- ... ...

    Abstract Background: Monovalent Omicron XBB.1.5-containing vaccines were approved for Coronavirus disease 2019 (COVID-19) 2023-2024 immunizations.
    Methods: This ongoing, open-label, phase 2/3 study evaluated mRNA-1273.815-monovalent (50-µg Omicron XBB.1.5-spike mRNA) and mRNA-1273.231-bivalent (25-µg each Omicron XBB.1.5- and BA.4/BA.5-spike mRNAs))vaccines, administered as 5th doses to adults who previously received a primary series, a 3rd dose of an original mRNA COVID-19 vaccine, and a 4th dose of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity results 29 days post-vaccination are reported.
    Results: Participants (randomized 1:1) received 50-µg mRNA-1273.815(n=50) or mRNA-1273.231(n=51); median (interquartile range) months from the prior BA.4/BA.5-bivalent dose were 8.2 (8.1-8.3) and 8.3 (8.1-8.4), respectively. Neutralizing antibody (nAb) increased from pre-booster levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants tested. Day 29 nAb fold-increases from pre-booster levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1 and D614G. The monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1 and JN.1 variants in a participant (n=20) subset, 15 days post-vaccination. Reactogenicity was similar to previously reported mRNA-1273 original and bivalent vaccines.
    Conclusions: XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants including JN.1, supporting the XBB.1.5-spike sequence selection for the 2023-2024 COVID-19 vaccine update.
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiae067
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  4. Article ; Online: Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results.

    Chalkias, Spyros / Whatley, Jordan L / Eder, Frank / Essink, Brandon / Khetan, Shishir / Bradley, Paul / Brosz, Adam / McGhee, Nichole / Tomassini, Joanne E / Chen, Xing / Zhao, Xiaoping / Sutherland, Andrea / Shen, Xiaoying / Girard, Bethany / Edwards, Darin K / Feng, Jing / Zhou, Honghong / Walsh, Stephen / Montefiori, David C /
    Baden, Lindsey R / Miller, Jacqueline M / Das, Rituparna

    Nature medicine

    2023  Volume 29, Issue 9, Page(s) 2325–2333

    Abstract: This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received ... ...

    Abstract This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of the Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with the ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups of adults who previously received mRNA-1273 as primary vaccination series and booster doses were enrolled in a sequential, nonrandomized manner and received single-second boosters of mRNA-1273 (n = 376) or bivalent mRNA-1273.222 (n = 511). Primary objectives were safety and the noninferiority or superiority of neutralizing antibody (nAb) responses against Omicron BA.4/BA.5 and ancestral SARS-CoV-2 with the D614G mutation (ancestral SARS-CoV-2 (D614G)), 28 days post boost. Superiority and noninferiority were based on prespecified success criteria (lower bounds of 95% CI > 1 and < 0.677, respectively) of the mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent Omicron BA.4/BA.5-containing mRNA-1273.222 elicited superior nAb responses against BA.4/BA.5 versus mRNA-1273 and noninferior responses against ancestral SARS-CoV-2 (D614G) at day 29 post boost in participants without detectable prior SARS-CoV-2 infection. Day 29 seroresponses against Omicron BA.4/BA.5 were higher for mRNA-1273.222 than for mRNA-1273 and similar against ancestral SARS-CoV-2 (D614G), both meeting noninferiority criterion. The safety profile of mRNA-1273.222 was similar to that previously reported for mRNA-1273 with no new safety concerns identified. Continued monitoring of neutralization and real-world vaccine effectiveness are needed as additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065.
    MeSH term(s) Adult ; Humans ; 2019-nCoV Vaccine mRNA-1273 ; Antibodies, Neutralizing ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; mRNA Vaccines ; SARS-CoV-2/genetics
    Chemical Substances 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; Antibodies, Neutralizing ; COVID-19 Vaccines ; mRNA Vaccines
    Language English
    Publishing date 2023-08-31
    Publishing country United States
    Document type Clinical Trial, Phase II ; Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-023-02517-y
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  5. Article ; Online: Safety and Immunogenicity of an Omicron BA.4/BA.5 Bivalent Vaccine against Covid-19

    Chalkias, Spyros / Whatley, Jordan / Eder, Frank / Essink, Brandon / Khetan, Shishar / Bradley, Paul / Brosz, Adam / McGhee, Nichole / Tomassini, Joanne E / Chen, Xing / Sutherland, Andrea / Shen, Xiaoying / Girard, Bethany / Edwards, Darin K / Feng, Jing / Zhou, Honghong / Walsh, Stephen R / Montefiori, David C / Baden, Lindsey R /
    Miller, Jacqueline M / Das, Rituparna

    medRxiv

    Abstract: Background Information on the safety and immunogenicity of the omicron BA.4/BA.5-containing bivalent booster mRNA-1273.222 are needed. Methods In this ongoing, phase 2/3 trial, 50-μg mRNA-1273.222 (25-μg each ancestral Wuhan-Hu-1 and omicron BA.4/BA.5 ... ...

    Abstract Background Information on the safety and immunogenicity of the omicron BA.4/BA.5-containing bivalent booster mRNA-1273.222 are needed. Methods In this ongoing, phase 2/3 trial, 50-μg mRNA-1273.222 (25-μg each ancestral Wuhan-Hu-1 and omicron BA.4/BA.5 spike mRNAs) is compared to 50-μg mRNA-1273, administered as second boosters in adults who previously received a 2-injection (100-μg) primary series and first booster (50-μg) dose of mRNA-1273. The primary objectives were safety and immunogenicity 28 days post-boost. Results Participants received 50-μg of mRNA-1273 (n=376) or mRNA-1273.222 (n=511) as second booster doses. Omicron BA.4/BA.5 and ancestral SARS-CoV-2 D614G neutralizing antibody geometric mean titers (GMTs [95% confidence interval]) after mRNA-1273.222 (2324.6 [1921.2-2812.7] and 7322.4 [6386.2-8395.7]) were significantly higher than mRNA-1273 (488.5 [427.4-558.4] and 5651.4 (5055.7-6317.3) respectively, at day 29 post-boost in participants with no prior SARS-CoV-2-infection. A randomly selected subgroup (N=60) of participants in the mRNA-1273.222 group also exhibited cross-neutralization against the emerging omicron variants BQ.1.1 and XBB.1. No new safety concerns were identified with mRNA-1273.222. Vaccine effectiveness was not assessed in this study; in an exploratory analysis 1.6% of mRNA-1273.222 recipients had Covid-19 post-boost. Conclusion The bivalent omicron BA.4/BA.5-containing vaccine mRNA-1273.222 elicited superior neutralizing antibody responses against BA.4/BA.5 compared to mRNA-1273, with no safety concerns identified.
    Keywords covid19
    Language English
    Publishing date 2022-12-13
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.12.11.22283166
    Database COVID19

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  6. Article ; Online: Pig Fetal Septal Neurons Implanted into the Hippocampus of Aged or Cholinergic Deafferented Rats Grow Axons and Form Cross-Species Synapses in Appropriate Target Regions

    Terrence Deacon / Brandi Whatley / Celeste Leblanc / Ling Lin / Ole Isacson

    Cell Transplantation, Vol

    1999  Volume 8

    Abstract: The anatomical specificity of axon growth from fetal pig septal xenografts was studied by transplanting septal cells from E30–35 pig fetuses into cholinergic deafferented (192-IgG-saporin-infused) rats or into aged rats (> 18 months). Cell suspensions ( ... ...

    Abstract The anatomical specificity of axon growth from fetal pig septal xenografts was studied by transplanting septal cells from E30–35 pig fetuses into cholinergic deafferented (192-IgG-saporin-infused) rats or into aged rats (> 18 months). Cell suspensions (100,000 cells/μl) were injected bilaterally into the dorsal and ventral hippocampus of immunosuppresed rats (10 mg/kg/day cyclosporine A). To assess axonal growth and synapse formation, acetylcholinesterase histochemistry, an antibody to choline acetyltransferase (ChAT), and three pig-positive/rat-negative antibodies: bovine 70kD neurofilament (NF70), human low-affinity NGF receptor (hNGFr), and human synaptobrevin (hSB) were used. In rats with surviving grafts at 6 months, NF70 axonal labeling was more extensive than either ChAT or hNGFr labeling. All three markers demonstrated graft axons extending selectively through the hippocampal CA fields and the molecular layer of the dentate gyrus. Graft axons did not extend into adjacent entorhinal cortex or neocortex. The distribution of pig hSB-positive synapses correlated with AChE-positive fiber outgrowth in to the host. Electron microscopic analysis of hSB-immunostained hippocampal sections revealed pig presynaptic terminals in contact with normal rat postsynaptic structures in the CA fields and the dentate gyrus. These data demonstrate target-appropriate growth of pig cholinergic axons and the formation of cross-species synapses in the deafferented or aged rat hippocampus.
    Keywords Medicine ; R
    Subject code 630
    Language English
    Publishing date 1999-01-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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