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Article: Regulation of cardiac fibroblast cell death by unfolded protein response signaling.

Rowland, Mary B / Moore, Patrick E / Correll, Robert N

2024 Volume 14, Page(s) 1304669

Abstract: The endoplasmic reticulum (ER) is a tightly regulated organelle that requires specific environmental properties to efficiently carry out its function as a major site of protein synthesis and folding. Embedded in the ER membrane, ER stress sensors ... ...

Abstract	The endoplasmic reticulum (ER) is a tightly regulated organelle that requires specific environmental properties to efficiently carry out its function as a major site of protein synthesis and folding. Embedded in the ER membrane, ER stress sensors inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) serve as a sensitive quality control system collectively known as the unfolded protein response (UPR). In response to an accumulation of misfolded proteins, the UPR signals for protective mechanisms to cope with the cellular stress. Under prolonged unstable conditions and an inability to regain homeostasis, the UPR can shift from its original adaptive response to mechanisms leading to UPR-induced apoptosis. These UPR signaling pathways have been implicated as an important feature in the development of cardiac fibrosis, but identifying effective treatments has been difficult. Therefore, the apoptotic mechanisms of UPR signaling in cardiac fibroblasts (CFs) are important to our understanding of chronic fibrosis in the heart. Here, we summarize the maladaptive side of the UPR, activated downstream pathways associated with cell death, and agents that have been used to modify UPR-induced apoptosis in CFs.
Language	English
Publishing date	2024-01-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1304669
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Article ; Online: Assessing wound closure in mice using skin-punch biopsy.

Rowland, Mary B / Moore, Patrick E / Bui, Chuong / Correll, Robert N

STAR protocols

2023 Volume 4, Issue 1, Page(s) 101989

Abstract: Defects in myofibroblast function may cause wound healing defects in a variety of tissue types. Here we describe a simple skin-punch biopsy approach to screen mouse models for defects in wound closure that does not require extensive surgical training or ... ...

Abstract	Defects in myofibroblast function may cause wound healing defects in a variety of tissue types. Here we describe a simple skin-punch biopsy approach to screen mouse models for defects in wound closure that does not require extensive surgical training or expensive equipment. Experimental results may serve as an initial proof of concept to determine whether further investigation is necessary or if defects in myofibroblast function observed in other systems also result in reduced skin wound healing.
MeSH term(s)	Mice ; Animals ; Skin/diagnostic imaging ; Skin/pathology ; Wound Healing ; Biopsy ; Disease Models, Animal
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101989
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Article ; Online: Training for Success.

Correll, Robert N

Circulation research

2017 Volume 121, Issue 5, Page(s) 488–489

MeSH term(s)	Biomedical Research/education ; Biomedical Research/trends ; Career Choice ; Humans ; Laboratory Personnel/education ; Laboratory Personnel/trends
Language	English
Publishing date	2017-08-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.117.311363
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Article ; Online: The Clinician's Tardive Inventory (CTI): A New Clinical Tool for Documenting and Rating Tardive Dyskinesia.

Trosch, Richard M / Comella, Cynthia L / Caroff, Stanley N / Ondo, William G / Shillington, Alicia C / LaChappelle, Brandon J / Hauser, Robert A / Correll, Christoph U / Friedman, Joseph H

The Journal of clinical psychiatry

2024 Volume 85, Issue 1

Abstract: Objective:: Methods:: Results:: Conclusions: ...

Abstract	Objective: Methods: Results: Conclusions:
MeSH term(s)	Humans ; Tardive Dyskinesia/chemically induced ; Tardive Dyskinesia/diagnosis ; Activities of Daily Living ; Reproducibility of Results ; Movement Disorders ; Consensus
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	716287-x
ISSN	1555-2101 ; 0160-6689
ISSN (online)	1555-2101
ISSN	0160-6689
DOI	10.4088/JCP.23m14886
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Article ; Online: CaMKII does it again: even the mitochondria cannot escape its influence.

Correll, Robert N / Molkentin, Jeffery D

Circulation research

2013 Volume 112, Issue 9, Page(s) 1208–1211

Language	English
Publishing date	2013-04-26
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.113.301263
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Article: Personal and Social Functioning and Health-Related Quality of Life in Patients with Schizophrenia Treated with the Long-Acting Injectable Antipsychotic Risperidone ISM.

Litman, Robert / Naber, Dieter / Anta, Lourdes / Martínez, Javier / Filts, Yuriy / Correll, Christoph U

Neuropsychiatric disease and treatment

2023 Volume 19, Page(s) 219–232

Abstract: ... weeks with once-monthly (every 28 days) intramuscular Risperidone ISM 75 mg or 100 mg (n = 288), or ... placebo (n = 145), as well as 174 patients transitioning from the DB to an open-label 52-week extension ...

Abstract	Objective: To analyze the effect of Risperidone ISM on social functioning and health-related quality of life (HR-QoL) in both short- and long-term treatment of patients with schizophrenia. Patients and methods: This analysis was based on data from both phases of the PRISMA-3 study, including 433 relapsed patients from the double-blind (DB) phase of the PRISMA-3 trial who were treated for 12-weeks with once-monthly (every 28 days) intramuscular Risperidone ISM 75 mg or 100 mg (n = 288), or placebo (n = 145), as well as 174 patients transitioning from the DB to an open-label 52-week extension (OLE) phase, plus 41 de novo patients treated on a stable maintenance dose of oral risperidone. The clinician-administered Personal and Social Performance (PSP) scale and the patient-reported 20-item Subjective Well-being under Neuroleptics scale (SWN-20) were used to measure social functioning and HR-QoL outcomes, respectively. Results: Risperidone ISM significantly improved PSP total score from baseline to endpoint (Day 85) versus placebo in the DB phase with mean change total score (95% CI) of 10.7 (9; 12) compared to 4.8 (3; 7) for placebo (p < 0.0001). The statistically significant improvement was present from the first measurement time point (Day 29). SWN-20-measured HR-QoL increased on average in patients treated with Risperidone ISM in the DB phase. A significant improvement was also observed for PSP and SWN-20 scores from the OLE baseline to week 52 for patients transitioning from the DB phase. Stable de novo patients maintained similar PSP and SWN-20 scores during the whole OLE phase. Conclusion: Risperidone ISM provided a rapid and sustained improvement in personal and social functioning, and HR-QOL without need of oral risperidone supplementation or loading doses. These findings, along with a fast onset of efficacy, could contribute to reinforcing the therapeutic alliance and possibly an earlier discharge. Moreover, patient functioning continued improving or was maintained with long-term treatment.
Language	English
Publishing date	2023-01-25
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2186503-6
ISSN	1178-2021 ; 1176-6328
ISSN (online)	1178-2021
ISSN	1176-6328
DOI	10.2147/NDT.S392351
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Article ; Online: Overlapping and differential functions of ATF6α versus ATF6β in the mouse heart.

Correll, Robert N / Grimes, Kelly M / Prasad, Vikram / Lynch, Jeffrey M / Khalil, Hadi / Molkentin, Jeffery D

Scientific reports

2019 Volume 9, Issue 1, Page(s) 2059

Abstract: ... the transcriptionally active N-terminus of ATF6α or ATF6β revealed that these factors control overlapping gene expression ...

Abstract	Hemodynamic stress on the mammalian heart results in compensatory hypertrophy and activation of the unfolded protein response through activating transcription factor 6α (ATF6α) in cardiac myocytes, but the roles of ATF6α or the related transcription factor ATF6β in regulating this hypertrophic response are not well-understood. Here we examined the effects of loss of ATF6α or ATF6β on the cardiac response to pressure overload. Mice gene-deleted for Atf6 or Atf6b were subjected to 2 weeks of transverse aortic constriction, and each showed a significant reduction in hypertrophy with reduced expression of endoplasmic reticulum (ER) stress-associated proteins compared with controls. However, with long-term pressure overload both Atf6 and Atf6b null mice showed enhanced decompensation typified by increased heart weight, pulmonary edema and reduced function compared to control mice. Our subsequent studies using cardiac-specific transgenic mice expressing the transcriptionally active N-terminus of ATF6α or ATF6β revealed that these factors control overlapping gene expression networks that include numerous ER protein chaperones and ER associated degradation components. This work reveals previously unappreciated roles for ATF6α and ATF6β in regulating the pressure overload induced cardiac hypertrophic response and in controlling the expression of genes that condition the ER during hemodynamic stress.
MeSH term(s)	Activating Transcription Factor 6/metabolism ; Animals ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/physiology ; Female ; Heart/physiology ; Hemodynamics/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Transcription Factors/metabolism ; Unfolded Protein Response/physiology
Chemical Substances	Activating Transcription Factor 6 ; Atf6 protein, mouse ; Atf6b protein, mouse ; Transcription Factors
Language	English
Publishing date	2019-02-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-39515-5
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Article ; Online: Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis.

Brody, Matthew J / Vanhoutte, Davy / Bakshi, Chinmay V / Liu, Ruije / Correll, Robert N / Sargent, Michelle A / Molkentin, Jeffery D

The Journal of biological chemistry

2019 Volume 294, Issue 22, Page(s) 8918–8929

Abstract: Valosin-containing protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum- ... ...

Abstract	Valosin-containing protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum-associated degradation (ERAD) pathway. However, how VCP functions in the heart has not been carefully examined despite the fact that human mutations in VCP cause Paget disease of bone and frontotemporal dementia, an autosomal dominant multisystem proteinopathy that includes disease in the heart, skeletal muscle, brain, and bone. Here we generated heart-specific transgenic mice overexpressing WT VCP or a VCP
MeSH term(s)	Animals ; Cardiomyopathies/metabolism ; Cardiomyopathies/pathology ; Cells, Cultured ; Endoplasmic Reticulum-Associated Degradation ; Heart/physiology ; Lamins/metabolism ; Mice ; Mice, Transgenic ; Mutagenesis, Site-Directed ; Myocardium/metabolism ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Nuclear Proteins/metabolism ; Protein Subunits/metabolism ; RNA-Binding Proteins/metabolism ; Rats ; Ribosomal Proteins/metabolism ; Ubiquitination ; Valosin Containing Protein/genetics ; Valosin Containing Protein/metabolism
Chemical Substances	Lamins ; Nuclear Proteins ; Protein Subunits ; RNA-Binding Proteins ; Ribosomal Proteins ; Valosin Containing Protein (EC 3.6.4.6)
Language	English
Publishing date	2019-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.007585
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Article ; Online: Pioglitazone improves working memory performance when administered in chronic TBI.

McGuire, Jennifer L / Correll, Erika A / Lowery, Alexandra C / Rhame, Katherine / Anwar, Fatima N / McCullumsmith, Robert E / Ngwenya, Laura B

Neurobiology of disease

2019 Volume 132, Page(s) 104611

Abstract: Traumatic brain injury (TBI) is a leading cause of long-term disability in the United States. Even in comparatively mild injuries, cognitive and behavioral symptoms can persist for years, and there are currently no established strategies for mitigating ... ...

Abstract	Traumatic brain injury (TBI) is a leading cause of long-term disability in the United States. Even in comparatively mild injuries, cognitive and behavioral symptoms can persist for years, and there are currently no established strategies for mitigating symptoms in chronic injury. A key feature of TBI-induced damage in acute and chronic injury is disruption of metabolic pathways. As neurotransmission, and therefore cognition, are highly dependent on the supply of energy, we hypothesized that modulating metabolic activity could help restore behavioral performance even when treatment was initiated weeks after TBI. We treated rats with pioglitazone, a FDA-approved drug for diabetes, beginning 46 days after lateral fluid percussion injury and tested working memory performance in the radial arm maze (RAM) after 14 days of treatment. Pioglitazone treated TBI rats performed significantly better in the RAM test than untreated TBI rats, and similarly to control animals. While hexokinase activity in hippocampus was increased by pioglitazone treatment, there was no upregulation of either the neuronal glucose transporter or hexokinase enzyme expression. Expression of glial markers GFAP and Iba-1 were also not influenced by pioglitazone treatment. These studies suggest that targeting brain metabolism, in particular hippocampal metabolism, may be effective in alleviating cognitive symptoms in chronic TBI.
MeSH term(s)	Animals ; Brain/drug effects ; Brain Injuries, Traumatic ; Chronic Disease ; Male ; Maze Learning/drug effects ; Memory, Short-Term/drug effects ; Pioglitazone/pharmacology ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Pioglitazone (X4OV71U42S)
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2019.104611
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Book ; Online: High-bandwidth nonlinear control for soft actuators with recursive network models

Manzano, Sarah Aguasvivas / Xu, Patricia / Ly, Khoi / Shepherd, Robert / Correll, Nikolaus

2021

Abstract: We present a high-bandwidth, lightweight, and nonlinear output tracking technique for soft actuators that combines parsimonious recursive layers for forward output predictions and online optimization using Newton-Raphson. This technique allows for ... ...

Abstract	We present a high-bandwidth, lightweight, and nonlinear output tracking technique for soft actuators that combines parsimonious recursive layers for forward output predictions and online optimization using Newton-Raphson. This technique allows for reduced model sizes and increased control loop frequencies when compared with conventional RNN models. Experimental results of this controller prototype on a single soft actuator with soft positional sensors indicate effective tracking of referenced spatial trajectories and rejection of mechanical and electromagnetic disturbances. These are evidenced by root mean squared path tracking errors (RMSE) of 1.8mm using a fully connected (FC) substructure, 1.62mm using a gated recurrent unit (GRU) and 2.11mm using a long short term memory (LSTM) unit, all averaged over three tasks. Among these models, the highest flash memory requirement is 2.22kB enabling co-location of controller and actuator. Comment: International Symposium on Experimental Robotics (ISER) 2020, Malta
Keywords	Computer Science - Robotics ; Computer Science - Artificial Intelligence ; Computer Science - Software Engineering ; Electrical Engineering and Systems Science - Systems and Control ; Mathematics - Numerical Analysis
Subject code	629
Publishing date	2021-01-04
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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