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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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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 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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Article ; Online: Tracking Molecular Diffusion across Biomaterials' Interfaces Using Stimulated Raman Scattering.

Cui, Han / Glidle, Andrew / Cooper, Jonathan M

ACS applied materials & interfaces

2022 Volume 14, Issue 28, Page(s) 31586–31593

Abstract: The determination of molecular diffusion across biomaterial interfaces, including those involving hydrogels and tissues remains important, underpinning the understanding of a broad range of processes including, for example, drug delivery. Current ... ...

Abstract	The determination of molecular diffusion across biomaterial interfaces, including those involving hydrogels and tissues remains important, underpinning the understanding of a broad range of processes including, for example, drug delivery. Current techniques using Raman spectroscopy have previously been established as a method to quantify diffusion coefficients, although when using spontaneous Raman spectroscopy, the signal can be weak and dominated by interferences such as background fluorescence (including biological autofluoresence). To overcome these issues, we demonstrate the use of the stimulated Raman scattering technique to obtain measurements in soft tissue samples that have good signal-to-noise ratios and are largely free from fluorescence interference. As a model illustration of a small metabolite/drug molecule being transported through tissue, we use deuterated (
MeSH term(s)	Biocompatible Materials ; Diffusion ; Hydrogels/chemistry ; Spectrum Analysis, Raman/methods
Chemical Substances	Biocompatible Materials ; Hydrogels
Language	English
Publishing date	2022-07-08
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.2c04444
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Article ; Online: Woman with ST Changes Following Days of Vomiting.

Hoang, Huy / Giordano, Jonathan A / Cooper, Benjamin L

Annals of emergency medicine

2021 Volume 77, Issue 4, Page(s) 442–444

MeSH term(s)	Aged ; Cardiac Catheterization ; Electrocardiography ; Emergency Service, Hospital ; Female ; Heart Diseases/etiology ; Heart Diseases/therapy ; Humans ; Hypokalemia/drug therapy ; Hypokalemia/etiology ; Magnesium Sulfate/therapeutic use ; Potassium/therapeutic use ; Vomiting/complications
Chemical Substances	Magnesium Sulfate (7487-88-9) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2021-03-25
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	603080-4
ISSN	1097-6760 ; 0196-0644
ISSN (online)	1097-6760
ISSN	0196-0644
DOI	10.1016/j.annemergmed.2020.08.034
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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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Article ; Online: Low Vision Impairs Implicit Sensorimotor Adaptation in Response to Small Errors, But Not Large Errors.

Tsay, Jonathan S / Tan, Steven / Chu, Marlena A / Ivry, Richard B / Cooper, Emily A

Journal of cognitive neuroscience

2023 Volume 35, Issue 4, Page(s) 736–748

Abstract: Successful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (e.g., where you see your hand after reaching vs. where ... ...

Abstract	Successful goal-directed actions require constant fine-tuning of the motor system. This fine-tuning is thought to rely on an implicit adaptation process that is driven by sensory prediction errors (e.g., where you see your hand after reaching vs. where you expected it to be). Individuals with low vision experience challenges with visuomotor control, but whether low vision disrupts motor adaptation is unknown. To explore this question, we assessed individuals with low vision and matched controls with normal vision on a visuomotor task designed to isolate implicit adaptation. We found that low vision was associated with attenuated implicit adaptation only for small visual errors, but not for large visual errors. This result highlights important constraints underlying how low-fidelity visual information is processed by the sensorimotor system to enable successful implicit adaptation.
MeSH term(s)	Humans ; Vision, Low ; Hand
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1007410-7
ISSN	1530-8898 ; 0898-929X ; 1096-8857
ISSN (online)	1530-8898
ISSN	0898-929X ; 1096-8857
DOI	10.1162/jocn_a_01969
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Article ; Online: Cas phosphorylation regulates focal adhesion assembly.

Kumar, Saurav / Stainer, Amanda / Dubrulle, Julien / Simpkins, Christopher / Cooper, Jonathan A

eLife

2023 Volume 12

Abstract: Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) ... ...

Abstract	Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) substrate Cas (Crk-associated substrate, p130Cas, BCAR1) is phosphorylated and associated with its Crk/CrkL effectors in clusters that are precursors of focal adhesions. The initial phospho-Cas clusters contain integrin β1 in its inactive, bent closed, conformation. Later, phospho-Cas and total Cas levels decrease as integrin β1 is activated and core focal adhesion proteins including vinculin, talin, kindlin, and paxillin are recruited. Cas is required for cell spreading and focal adhesion assembly in epithelial and fibroblast cells on collagen and fibronectin. Cas cluster formation requires Cas, Crk/CrkL, SFKs, and Rac1 but not vinculin. Rac1 provides positive feedback onto Cas through reactive oxygen, opposed by negative feedback from the ubiquitin proteasome system. The results suggest a two-step model for focal adhesion assembly in which clusters of phospho-Cas, effectors and inactive integrin β1 grow through positive feedback prior to integrin activation and recruitment of core focal adhesion proteins.
MeSH term(s)	Phosphorylation ; Focal Adhesions/metabolism ; Phosphoproteins/metabolism ; Integrin beta1/metabolism ; Crk-Associated Substrate Protein/metabolism ; Protein-Tyrosine Kinases/metabolism ; Integrins/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Focal Adhesion Kinase 1/metabolism
Chemical Substances	Phosphoproteins ; Integrin beta1 ; Crk-Associated Substrate Protein ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Integrins ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; Focal Adhesion Kinase 1 (EC 2.7.10.2)
Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.90234
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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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Article ; Online: Exploring the barriers to, and importance of, participant diversity in early-phase clinical trials: an interview-based qualitative study of professionals and patient and public representatives.

Chatters, Robin / Dimairo, Munyaradzi / Cooper, Cindy / Ditta, Shamila / Woodward, Jonathan / Biggs, Katie / Ogunleye, Della / Thistlethwaite, Fiona / Yap, Christina / Rothman, Alexander

BMJ open

2024 Volume 14, Issue 3, Page(s) e075547

Abstract: Objectives: To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.: Design: Qualitative interviews analysed using thematic analysis.: Setting and participants: Five professionals (clinical researchers ... ...

Abstract	Objectives: To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials. Design: Qualitative interviews analysed using thematic analysis. Setting and participants: Five professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022. Participants were identified via their institutional web page, existing contacts or social media (eg, X, formerly known as Twitter). Results: Professionals viewed that diversity is not currently considered in all early-phase clinical trials but felt that it should always be taken into account. Such trials are primarily undertaken at a small number of centres, thus limiting the populations they can access. Referrals from clinicians based in the community may increase diversity; however, those referred are often not from underserved groups. Referrals may be hindered by the extra resources required to approach and recruit underserved groups and participants often having to undertake 'self-driven' referrals. Patient and public representatives stated that diversity is important in research staff and that potential participants should be informed of the need for diversity. Those from underserved groups may require clarification regarding the potential harms of a treatment, even if these are unknown. Education may improve awareness and perception of early-phase clinical trials. We provide 14 recommendations to improve diversity in early-phase clinical trials. Conclusions: Diversity should be considered in all early-phase trials. Consideration is required regarding the extent of diversity and how it is addressed. The increased resources needed to recruit those from underserved groups may warrant funders to increase the funds to support the recruitment of such participants. The potential harms and societal benefits of the research should be presented to potential participants in a balanced but accurate way to increase transparency.
MeSH term(s)	Humans ; Ethnicity ; Minority Groups ; Qualitative Research ; Educational Status ; Social Media
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-075547
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Article ; Online: Use it or lose it: protecting ageing muscles with lifelong recreational exercise.

Aguilera, Jonathan A / Pourhashemi, Nicki / Sharpe, Cooper J / Friesen, Beata

The Journal of physiology

2022 Volume 600, Issue 15, Page(s) 3397–3398

MeSH term(s)	Aging/physiology ; Humans ; Muscle, Skeletal/physiology ; Muscles ; Sarcopenia/pathology
Language	English
Publishing date	2022-07-17
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP283338
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