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  1. Article: Denitrative Sulfonylation of Nitroarenes with Sodium Sulfinates

    Da Luz, Jonathan / Čierna, Michaela / Cooper, Bradley D. / Harris, Thomas D. / Lim, Ethan R. X. / Carney, Jonathan R. / James, Michael J.

    Synthesis

    2024  

    Abstract: A one-step method to convert nitroarenes into aryl sulfones under operationally simple, transition-metal-free conditions is described. A range of nitroarenes were reacted with sodium sulfinates and caesium carbonate in N N ′-dimethylpropyleneurea to ... ...

    Abstract A one-step method to convert nitroarenes into aryl sulfones under operationally simple, transition-metal-free conditions is described. A range of nitroarenes were reacted with sodium sulfinates and caesium carbonate in N N ′-dimethylpropyleneurea to afford aryl sulfones in up to 83% yield.
    Keywords denitrative functionalisation ; sulfonylation ; nitroarenes ; aryl sulfones ; transition-metal-free
    Language English
    Publishing date 2024-03-27
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2033062-5
    ISSN 1437-210X ; 0039-7881
    ISSN (online) 1437-210X
    ISSN 0039-7881
    DOI 10.1055/a-2295-8639
    Database Thieme publisher's database

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  2. Article: Top-down and bottom-up propagation of disease in the neuronal ceroid lipofuscinoses.

    Ostergaard, John R / Nelvagal, Hemanth R / Cooper, Jonathan D

    Frontiers in neurology

    2022  Volume 13, Page(s) 1061363

    Abstract: Background: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related ... ...

    Abstract Background: The Neuronal Ceroid Lipofuscinoses (NCLs) may be considered distinct neurodegenerative disorders with separate underlying molecular causes resulting from monogenetic mutations. An alternative hypothesis is to consider the NCLs as related diseases that share lipofuscin pathobiology as the common core feature, but otherwise distinguished by different a) initial anatomic location, and b) disease propagation.
    Methods: We have tested this hypothesis by comparing known differences in symptomatology and pathology of the CLN1 phenotype caused by complete loss of
    Results: Despite displaying similar pathological endpoints, the clinical phenotypes and the evidence of imaging and
    Discussion: The propagation of disease in these two NCLs therefore has much in common with the "Brain-first" vs. "Body-first" models of alpha-synuclein propagation in Parkinson's disease. CLN1 disease represents a "Body-first" or bottom-up disease propagation and CLN3 disease having a "Brain-first" and top-down propagation. It is noteworthy that the varied phenotypes of CLN1 disease, whether it starts in infancy (infantile form) or later in childhood (juvenile form), still fit with our proposed hypothesis of a bottom-up disease propagation in CLN1. Likewise, in protracted CLN3 disease, where both cognitive and motor declines are delayed, the initial manifestations of disease are also seen in the outer retinal layers, i.e., identical to classical Juvenile NCL disease.
    Language English
    Publishing date 2022-11-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2022.1061363
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  3. Article ; Online: Future perspectives: What lies ahead for Neuronal Ceroid Lipofuscinosis research?

    Cooper, Jonathan D / Mole, Sara E

    Biochimica et biophysica acta. Molecular basis of disease

    2020  Volume 1866, Issue 9, Page(s) 165681

    Abstract: Progress is being made in all aspects of Neuronal Ceroid Lipofuscinosis (NCL) research, resulting in many recent advances. These advances encompass several areas that were previously thought intractable, ranging from basic science, through to a better ... ...

    Abstract Progress is being made in all aspects of Neuronal Ceroid Lipofuscinosis (NCL) research, resulting in many recent advances. These advances encompass several areas that were previously thought intractable, ranging from basic science, through to a better understanding of the clinical presentation of different forms of NCL, therapeutic development, and new clinical trials that are underway. Increasing numbers of original NCL research papers continue to be published, and this new sense of momentum is greatly encouraging for the field. Here, we make some predictions as to what we can anticipate in the next few years.
    MeSH term(s) Animals ; Biomedical Research ; Disease Models, Animal ; Genetic Therapy ; Humans ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/pathology ; Neuronal Ceroid-Lipofuscinoses/therapy
    Language English
    Publishing date 2020-01-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 60-7
    ISSN 1879-260X ; 1879-2596 ; 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) 1879-260X ; 1879-2596 ; 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.2020.165681
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  4. Article ; Online: Fipronil Affects Craniofacial and Heart Development in Zebrafish Embryos (

    Cooper, Kasey L / Krut, Zoe G / Franz, Bennet D / Walker, Benjamin S / Kramer, Alexander G / Morgan, Jonathan R / Lassiter, Christopher S

    Zebrafish

    2024  Volume 21, Issue 2, Page(s) 181–190

    Abstract: Fipronil is a broad-spectrum insecticide that has off-target effects in developing vertebrate embryos. In this study, we investigate treatment of zebrafish embryos with fipronil over the course of 5 days and examine the effects on body length, the ... ...

    Abstract Fipronil is a broad-spectrum insecticide that has off-target effects in developing vertebrate embryos. In this study, we investigate treatment of zebrafish embryos with fipronil over the course of 5 days and examine the effects on body length, the cardiovascular system, and craniofacial morphology. We found the insecticide caused shorter body length and a decrease in eye size. By examining specific heart chamber morphology, as well as jaw angle and length, we quantified defects including enlargement of the heart and increases in jaw length and width. Further studies are needed to assess the mechanisms of fipronil's effect on vertebrate development for both environmental and human health concerns.
    MeSH term(s) Animals ; Humans ; Zebrafish ; Insecticides/toxicity ; Embryo, Nonmammalian ; Pyrazoles/toxicity ; Water Pollutants, Chemical
    Chemical Substances Insecticides ; fipronil (QGH063955F) ; Pyrazoles ; Water Pollutants, Chemical
    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2156020-1
    ISSN 1557-8542 ; 1545-8547
    ISSN (online) 1557-8542
    ISSN 1545-8547
    DOI 10.1089/zeb.2023.0055
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  5. Article ; Online: Improved simulated ventilation with a novel tidal volume and peak inspiratory pressure controlling bag valve mask: A pilot study.

    Merrell, Jonathan G / Scott, Adam C / Stambro, Ryan / Boukai, Amit / Cooper, Dylan D

    Resuscitation plus

    2023  Volume 13, Page(s) 100350

    Abstract: Introduction: The dangers of hyperventilation during resuscitation are well known. Traditional bag valve mask (BVM) devices rely on end users to control tidal volume (V: Methods: Senior emergency medicine residents and fellows participated in a three- ...

    Abstract Introduction: The dangers of hyperventilation during resuscitation are well known. Traditional bag valve mask (BVM) devices rely on end users to control tidal volume (V
    Methods: Senior emergency medicine residents and fellows participated in a three-phase simulation study. First, participants used the Ambu Spur II BVM in adult and pediatric resuscitations. V
    Results: Nineteen participants were included in the adult arm of the study, and 16 in the pediatric arm. The BBVM restricted V
    Conclusion: The BBVM exceeded the Ambu Spur II in delivering appropriate V
    Language English
    Publishing date 2023-01-05
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-5204
    ISSN (online) 2666-5204
    DOI 10.1016/j.resplu.2022.100350
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  6. Article: Rising to the challenge of defining and operationalising multimorbidity in a UK hospital setting: the ADMISSION research collaborative.

    Cooper, Rachel / Bunn, Jonathan G / Richardson, Sarah J / Hillman, Susan J / Sayer, Avan A / Witham, Miles D

    European geriatric medicine

    2024  

    Abstract: Purpose: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of ... ...

    Abstract Purpose: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of multimorbidity in hospitals; (2) apply these principles and identify a list of long-term conditions; (3) operationalise this list by mapping it to International Classification of Diseases 10th revision (ICD-10) codes.
    Methods: Review by independent assessors and ratification by an interdisciplinary programme management group.
    Results: Agreement was reached that when defining multimorbidity in hospitals for research purposes all conditions must meet the following four criteria: (1) medical diagnosis; (2) typically present for ≥ 12 months; (3) at least one of currently active; permanent in effect; requiring current treatment, care or therapy; requiring surveillance; remitting-relapsing and requiring ongoing treatment or care, and; (4) lead to at least one of: significantly increased risk of death; significantly reduced quality of life; frailty or physical disability; significantly worsened mental health; significantly increased treatment burden (indicated by an increased risk of hospital admission or increased length of hospital stay). Application of these principles to two existing lists of conditions led to the selection of 60 conditions that can be used when defining multimorbidity for research focused on hospitalised patients. ICD-10 codes were identified for each of these conditions to ensure consistency in their operationalisation.
    Conclusions: This work contributes to achieving the goal of greater transparency and consistency in the approach to the study of multimorbidity, with a specific focus on the UK hospital setting.
    Language English
    Publishing date 2024-03-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2556794-9
    ISSN 1878-7657 ; 1878-7649
    ISSN (online) 1878-7657
    ISSN 1878-7649
    DOI 10.1007/s41999-024-00953-8
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  7. Article: N-cadherin dynamically regulates pediatric glioma cell migration in complex environments.

    Kim, Dayoung / Olson, James M / Cooper, Jonathan A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow ... ...

    Abstract Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood. N-cadherin is highly expressed in pediatric gliomas and associated with shorter survival. We found that inter-cellular homotypic N-cadherin interactions differentially regulate glioma migration according to the microenvironment, stimulating migration on cultured neurons or astrocytes but inhibiting invasion into reconstituted or astrocyte-deposited extracellular matrix. N-cadherin localizes to filamentous connections between migrating leader cells but to epithelial-like junctions between followers. Leader cells have more surface and recycling N-cadherin, increased YAP1/TAZ signaling, and increased proliferation relative to followers. YAP1/TAZ signaling is dynamically regulated as leaders and followers change position, leading to altered N-cadherin levels and organization. Together, the results suggest that pediatric glioma cells adapt to different microenvironments by regulating N-cadherin dynamics and cell-cell contacts.
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.04.535599
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  8. Article ; Online: N-cadherin dynamically regulates pediatric glioma cell migration in complex environments.

    Kim, Dayoung / Olson, James M / Cooper, Jonathan A

    The Journal of cell biology

    2024  Volume 223, Issue 6

    Abstract: Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow ... ...

    Abstract Pediatric high-grade gliomas are highly invasive and essentially incurable. Glioma cells migrate between neurons and glia, along axon tracts, and through extracellular matrix surrounding blood vessels and underlying the pia. Mechanisms that allow adaptation to such complex environments are poorly understood. N-cadherin is highly expressed in pediatric gliomas and associated with shorter survival. We found that intercellular homotypic N-cadherin interactions differentially regulate glioma migration according to the microenvironment, stimulating migration on cultured neurons or astrocytes but inhibiting invasion into reconstituted or astrocyte-deposited extracellular matrix. N-cadherin localizes to filamentous connections between migrating leader cells but to epithelial-like junctions between followers. Leader cells have more surface and recycling N-cadherin, increased YAP1/TAZ signaling, and increased proliferation relative to followers. YAP1/TAZ signaling is dynamically regulated as leaders and followers change position, leading to altered N-cadherin levels and organization. Together, the results suggest that pediatric glioma cells adapt to different microenvironments by regulating N-cadherin dynamics and cell-cell contacts.
    MeSH term(s) Child ; Humans ; Astrocytes ; Axons ; Cadherins/metabolism ; Cell Movement ; Glioma/metabolism ; Glioma/pathology ; Tumor Microenvironment
    Chemical Substances Cadherins ; CDH2 protein, human
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202401057
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  9. Article: Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.

    Takahashi, Keigo / Nelvagal, Hemanth R / Lange, Jenny / Cooper, Jonathan D

    Frontiers in neurology

    2022  Volume 13, Page(s) 886567

    Abstract: While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will ... ...

    Abstract While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the central nervous system across NCL subtypes, revealing a wide range of glial responses to disease. The emerging evidence of glial dysfunction questions the traditional "neuron-centric" view of NCLs, and would suggest that directly targeting glia in addition to neurons could lead to better therapeutic outcomes. This review summarizes the most up-to-date understanding of glial pathologies and their contribution to the pathogenesis of NCLs, and highlights some of the associated challenges that require further research.
    Language English
    Publishing date 2022-04-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2022.886567
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  10. Article ; Online: Infographic. Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials.

    Edwards, Jamie J / Deenmamode, Algis H P / Griffiths, Megan / Arnold, Oliver / Cooper, Nicola J / Wiles, Jonathan D / O'Driscoll, Jamie M

    British journal of sports medicine

    2023  Volume 57, Issue 20, Page(s) 1335–1336

    Language English
    Publishing date 2023-08-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 600592-5
    ISSN 1473-0480 ; 0306-3674
    ISSN (online) 1473-0480
    ISSN 0306-3674
    DOI 10.1136/bjsports-2023-107513
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    Full text online

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