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  • 1
    Online Resource
    Online Resource
    Data_Sheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 15 ( 2022-1-24)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2022-1-24)
    Abstract: Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, for complex disorders such as Alzheimer’s disease (AD), the generation and availability of innumerous distinct animal models present unique challenges to AD researchers and hinder the success of useful therapies. Here, we conducted an in-depth analysis of the 3xTg-AD mouse model of AD across its lifespan to better inform the field of the various pathologies that appear at specific ages, and comment on drift that has occurred in the development of pathology in this line since its development 20 years ago. This modern characterization of the 3xTg-AD model includes an assessment of impairments in long-term potentiation followed by quantification of amyloid beta (Aβ) plaque burden and neurofibrillary tau tangles, biochemical levels of Aβ and tau protein, and neuropathological markers such as gliosis and accumulation of dystrophic neurites. We also present a novel comparison of the 3xTg-AD model with the 5xFAD model using the same deep-phenotyping characterization pipeline and show plasma NfL is strongly driven by plaque burden. The results from these analyses are freely available via the AD Knowledge Portal ( https://modeladexplorer.org/ ). Our work demonstrates the utility of a characterization pipeline that generates robust and standardized information relevant to investigating and comparing disease etiologies of current and future models of AD.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2021.785276
    DOI: 10.3389/fnins.2021.785276.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 2
    Online Resource
    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-6-14)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-6-14)
    Abstract: The field of lentiviral vector (LV) production continues to face challenges in large-scale manufacturing, specifically regarding producing enough vectors to meet the demand for treating patients as well as producing high and consistent quality of vectors for efficient dosing. Two areas of interest are the use of stable producer cell lines, which facilitates the scalability of LV production processes as well as making the process more reproducible and robust for clinical applications, and the search of a cell retention device scalable to industrial-size bioreactors. This manuscript investigates a stable producer cell line for producing LVs with GFP as the transgene at shake flask scale and demonstrates LV production at 3L bioreactor scale using the Tangential Flow Depth Filtration (TFDF) as a cell retention device in perfusion mode. Cumulative functional yields of 3.3 x 10 11 and 3.9 x 10 11 transducing units were achieved; the former over 6 days of LV production with 16.3 L of perfused media and the latter over 4 days with 16 L. In comparing to a previously published value that was achieved using the same stable producer cell line and the acoustic filter as the perfusion device at the same bioreactor scale, the TFDF perfusion run produced 1.5-fold higher cumulative functional yield. Given its scale-up potential, the TFDF is an excellent candidate to be further evaluated to determine optimized conditions that can ultimately support continuous manufacturing of LVs at large scale.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    URL: Article
    DOI: 10.3389/fbioe.2022.887716
    DOI: 10.3389/fbioe.2022.887716.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 3
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-21)
    Abstract: Antibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model. Methods Total IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1. Results The IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters. Discussion This study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1138629
    DOI: 10.3389/fimmu.2023.1138629.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    The Use of Tissue Engineering to Fabricate Perfusable 3D Brain Microvessels in vitro
    Frontiers Media SA ; 2021
    In:  Frontiers in Physiology Vol. 12 ( 2021-8-31)
    Details
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 12 ( 2021-8-31)
    Abstract: Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    URL: Article
    DOI: 10.3389/fphys.2021.715431
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564217-0
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  • 5
    Online Resource
    Online Resource
    Solving inherited white matter disorder etiologies in the neurology clinic: Challenges and lessons learned using next-generation sequencing
    Frontiers Media SA ; 2023
    In:  Frontiers in Neurology Vol. 14 ( 2023-4-3)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-4-3)
    Abstract: Rare neurodevelopmental disorders, including inherited white matter disorders or leukodystrophies, often present a diagnostic challenge on a genetic level given the large number of causal genes associated with a range of disease subtypes. This study aims to demonstrate the challenges and lessons learned in the genetic investigations of leukodystrophies through presentation of a series of cases solved using exome or genome sequencing. Methods Each of the six patients had a leukodystrophy associated with hypomyelination or delayed myelination on MRI, and inconclusive clinical diagnostic genetic testing results. We performed next generation sequencing (case-based exome or genome sequencing) to further investigate the genetic cause of disease. Results Following different lines of investigation, molecular diagnoses were obtained for each case, with patients harboring pathogenic variants in a range of genes including TMEM106B, GJA1, AGA, POLR3A , and TUBB4A . We describe the lessons learned in reaching the genetic diagnosis, including the importance of (a) utilizing proper multi-gene panels in clinical testing, (b) assessing the reliability of biochemical assays in supporting diagnoses, and (c) understanding the limitations of exome sequencing methods in regard to CNV detection and region coverage in GC-rich areas. Discussion This study illustrates the importance of applying a collaborative diagnostic approach by combining detailed phenotyping data and metabolic results from the clinical environment with advanced next generation sequencing analysis techniques from the research environment to increase the diagnostic yield in patients with genetically unresolved leukodystrophies.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2023.1148377
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 6
    Online Resource
    Online Resource
    Image_3.jpeg
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-12)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-12)
    Abstract: Infants acquire maternal antibodies by Fc receptor transcytosis across the placenta during pregnancy. Fc receptors are expressed on immune cells and are important for activation of effector cell functions. Methods In this study, we evaluated Fc receptor engagement and ADCC activity of plasma binding antibodies from human immunodeficiency virus-1 (HIV) -infected mothers and to identify factors that may contribute to protection from HIV vertical transmission. Results HIV-specific binding and Fc receptor engagement of plasma antibodies varied between mothers by transmission status and infants by infection status. Non-transmitting (NT) mothers and HIV-uninfected infants had antibodies with higher neonatal Fc receptor (FcRn) and FcγR engagement, as compared to transmitting (T) mothers and HIV+ infants, respectively. A significant inverse correlation between plasma antibody FcRn and FcγR engagement was observed for T mothers, but not NT mothers. Conversely, a significant direct correlation was observed between plasma antibody FcRn and FcγR engagement for HIV- infants, but not for HIV+ infants. Consequently, we observed significantly higher plasma antibody ADCC potency and breadth in HIV- infants, as compared to HIV+ infants. However, no differences in overall ADCC potency and breadth were observed between mothers. FcRn-engagement of HIV-specific antibodies in both mothers and infants predicted a lack of vertical transmission of HIV. Discussion This study indicates that HIV-uninfected infants acquire HIV-specific antibodies with greater Fc receptor engagement and thus, greater ADCC capacity.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1051501
    DOI: 10.3389/fimmu.2022.1051501.s001
    DOI: 10.3389/fimmu.2022.1051501.s002
    DOI: 10.3389/fimmu.2022.1051501.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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