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Article: ACE2 protein expression within isogenic cell lines is heterogeneous and associated with distinct transcriptomes.

Sherman, Emily J / Emmer, Brian T

bioRxiv : the preprint server for biology

2021

Abstract: The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, with ... ...

Abstract	The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, with investigation at the protein level limited by uncertain specificity of commercial ACE2 antibodies. Here, we report our development of a sensitive and specific flow cytometry-based assay for cellular ACE2 protein abundance. Application of this approach to multiple cell lines revealed an unexpected degree of cellular heterogeneity, with detectable ACE2 protein in only a subset of cells in each isogenic population. This heterogeneity was mediated at the mRNA level by transcripts predominantly initiated from the
Language	English
Publishing date	2021-03-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.26.437218
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: ACE2 protein expression within isogenic cell lines is heterogeneous and associated with distinct transcriptomes.

Sherman, Emily J / Emmer, Brian T

Scientific reports

2021 Volume 11, Issue 1, Page(s) 15900

Abstract	The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, with investigation at the protein level limited by uncertain specificity of commercial ACE2 antibodies. Here, we report our development of a sensitive and specific flow cytometry-based assay for cellular ACE2 protein abundance. Application of this approach to multiple cell lines revealed an unexpected degree of cellular heterogeneity, with detectable ACE2 protein in only a subset of cells in each isogenic population. This heterogeneity was mediated at the mRNA level by transcripts predominantly initiated from the ACE2 proximal promoter. ACE2 expression was heritable but not fixed over multiple generations of daughter cells, with gradual drift toward the original heterogeneous background. RNA-seq profiling identified distinct transcriptomes of ACE2-expressing relative cells to non-expressing cells, with enrichment in functionally related genes and transcription factor target sets. Our findings provide a validated approach for the specific detection of ACE2 protein at the surface of single cells, support an epigenetic mechanism of ACE2 gene regulation, and identify specific pathways associated with ACE2 expression in HuH7 cells.
MeSH term(s)	Angiotensin-Converting Enzyme 2/analysis ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; Cell Line ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; RNA, Messenger/genetics ; Receptors, Virus/analysis ; Receptors, Virus/genetics ; SARS-CoV-2/isolation & purification ; Transcriptome
Chemical Substances	RNA, Messenger ; Receptors, Virus ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-08-05
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/s41598-021-95308-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The bed nucleus of the stria terminalis in threat detection: task choice and rodent experience.

Sherman, Emily R / Thomas, Jasmine J / Cahill, Emma N

Emerging topics in life sciences

2022 Volume 6, Issue 5, Page(s) 457–466

Abstract: Behavioural reactivity to potential threat is used to experimentally refine models of anxiety symptoms in rodents. We present a short review of the literature tying the most commonly used tasks to model anxiety symptoms to functional recruitment of bed ... ...

Abstract	Behavioural reactivity to potential threat is used to experimentally refine models of anxiety symptoms in rodents. We present a short review of the literature tying the most commonly used tasks to model anxiety symptoms to functional recruitment of bed nucleus of the stria terminalis circuits (BNST). Using a review of studies that investigated the role of the BNST in anxiety-like behaviour in rodents, we flag the certain challenges for the field. These stem from inconsistent methods of reporting the neuroanatomical BNST subregions and the interpretations of specific behaviour across a wide variety of tasks as 'anxiety-like'. Finally, to assist in interpretation of the findings, we discuss the potential interactions between typically used 'anxiety' tasks of innate behaviour that are potentially modulated by the social and individual experience of the animal.
MeSH term(s)	Animals ; Rodentia ; Septal Nuclei
Language	English
Publishing date	2022-11-23
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2882721-1
ISSN	2397-8554 ; 2397-8554 ; 2397-8562
ISSN (online)	2397-8554
ISSN	2397-8554 ; 2397-8562
DOI	10.1042/ETLS20220002
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Article ; Online: No impairment of contextual fear memory consolidation by oxytocin receptor antagonism in male rats.

Sherman, Emily R / Li, Jialu / Cahill, Emma N

Physiology & behavior

2024 Volume 279, Page(s) 114545

Abstract: Oxytocin is a peptide released into brain regions associated with the processing of aversive memory and threat responses. Given the expression of oxytocin receptors across this vigilance surveillance system of the brain, we investigated whether ... ...

Abstract	Oxytocin is a peptide released into brain regions associated with the processing of aversive memory and threat responses. Given the expression of oxytocin receptors across this vigilance surveillance system of the brain, we investigated whether pharmacological antagonism of the receptor would impact contextual aversive conditioning and memory. Adult male rats were conditioned to form an aversive contextual memory. The effects of peripheral administration of either the competitive antagonist Atosiban or noncompetitive antagonist L-368,899 were compared to saline controls. Oxytocin receptor antagonism treatment did not significantly impact the consolidation of aversive contextual memory in any of the groups. We conclude that peripheral antagonism of oxytocin signalling did not impact the formation of aversive memory.
MeSH term(s)	Rats ; Male ; Animals ; Receptors, Oxytocin ; Memory Consolidation ; Oxytocin/pharmacology ; Fear/physiology ; Conditioning, Psychological/physiology
Chemical Substances	Receptors, Oxytocin ; Oxytocin (50-56-6)
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3907-x
ISSN	1873-507X ; 0031-9384
ISSN (online)	1873-507X
ISSN	0031-9384
DOI	10.1016/j.physbeh.2024.114545
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Article ; Online: ACE2 protein expression within isogenic cell lines is heterogeneous and associated with distinct transcriptomes

Emily J. Sherman / Brian T. Emmer

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, ...

Abstract	Abstract The membrane protein angiotensin-converting enzyme 2 (ACE2) is a physiologic regulator of the renin-angiotensin system and the cellular receptor for the SARS-CoV-2 virus. Prior studies of ACE2 expression have primarily focused on mRNA abundance, with investigation at the protein level limited by uncertain specificity of commercial ACE2 antibodies. Here, we report our development of a sensitive and specific flow cytometry-based assay for cellular ACE2 protein abundance. Application of this approach to multiple cell lines revealed an unexpected degree of cellular heterogeneity, with detectable ACE2 protein in only a subset of cells in each isogenic population. This heterogeneity was mediated at the mRNA level by transcripts predominantly initiated from the ACE2 proximal promoter. ACE2 expression was heritable but not fixed over multiple generations of daughter cells, with gradual drift toward the original heterogeneous background. RNA-seq profiling identified distinct transcriptomes of ACE2-expressing relative cells to non-expressing cells, with enrichment in functionally related genes and transcription factor target sets. Our findings provide a validated approach for the specific detection of ACE2 protein at the surface of single cells, support an epigenetic mechanism of ACE2 gene regulation, and identify specific pathways associated with ACE2 expression in HuH7 cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The effectiveness of psychological interventions for reducing poor body image in endometriosis, PCOS and other gynaecological conditions: a systematic review and meta-analysis.

Pehlivan, Melissa J / Sherman, Kerry A / Wuthrich, Viviana / Gandhi, Esther / Zagic, Dino / Kopp, Emily / Perica, Valentina

Health psychology review

2023 , Page(s) 1–28

Abstract: Gynaecological conditions (e.g., endometriosis, PCOS) result in bodily changes that negatively impact body image. Psychological interventions (e.g., CBT, psychoeducation) have shown promise in reviews with the general population for alleviating body ... ...

Abstract	Gynaecological conditions (e.g., endometriosis, PCOS) result in bodily changes that negatively impact body image. Psychological interventions (e.g., CBT, psychoeducation) have shown promise in reviews with the general population for alleviating body image concerns. This systematic review and meta-analysis aims to provide asynthesis of the impact of psychological interventions for reducing body image concerns for individuals with gynaecological conditions. Electronic databases were searched for relevant psychological intervention studies with body image outcomes. Twenty-one eligible studies were included in the systematic review (ten were included in a random-effects meta-analysis). Studies included participants (
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2364161-7
ISSN	1743-7202 ; 1743-7199
ISSN (online)	1743-7202
ISSN	1743-7199
DOI	10.1080/17437199.2023.2245020
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Article ; Online: Does Extended Reality Simulation Improve Surgical/Procedural Learning and Patient Outcomes When Compared With Standard Training Methods?: A Systematic Review.

Woodall, William J / Chang, Eugene H / Toy, Serkan / Lee, Deborah R / Sherman, Jonathan H / Liu, Matthew / Chen, Philip / Youner, Emily / Cooke, James / Lancaster, Andy / Gerberi, Danielle / Herur-Raman, Aalap

Simulation in healthcare : journal of the Society for Simulation in Healthcare

2024 Volume 19, Issue 1S, Page(s) S98–S111

Abstract: Introduction: The use of extended reality (XR) technologies, including virtual, augmented, and mixed reality, has increased within surgical and procedural training programs. Few studies have assessed experiential learning- and patient-based outcomes ... ...

Abstract	Introduction: The use of extended reality (XR) technologies, including virtual, augmented, and mixed reality, has increased within surgical and procedural training programs. Few studies have assessed experiential learning- and patient-based outcomes using XR compared with standard training methods. Methods: As a working group for the Society for Simulation in Healthcare, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a PICO strategy to perform a systematic review of 4238 articles to assess the effectiveness of XR technologies compared with standard training methods. Outcomes were grouped into knowledge, time-to-completion, technical proficiency, reactions, and patient outcomes. Because of study heterogeneity, a meta-analysis was not feasible. Results: Thirty-two studies met eligibility criteria: 18 randomized controlled trials, 7 comparative studies, and 7 systematic reviews. Outcomes of most studies included Kirkpatrick levels of evidence I-III (reactions, knowledge, and behavior), while few reported level IV outcomes (patient). The overall risk of bias was low. With few exceptions, included studies showed XR technology to be more effective than standard training methods in improving objective skills and performance, shortening procedure time, and receiving more positive learner ratings. However, XR use did not show significant differences in gained knowledge. Conclusions: Surgical or procedural XR training may improve technical skill development among trainees and is generally favored over standard training methods. However, there should be an additional focus on how skill development translates to clinically relevant outcomes. We recommend longitudinal studies to examine retention and transfer of training to clinical settings, methods to improve timely, adaptive feedback for deliberate practice, and cost analyses.
MeSH term(s)	Humans ; Computer Simulation ; Augmented Reality ; Problem-Based Learning ; Clinical Competence ; Physical Therapy Modalities ; Simulation Training
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	2223429-9
ISSN	1559-713X ; 1559-2332
ISSN (online)	1559-713X
ISSN	1559-2332
DOI	10.1097/SIH.0000000000000767
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Colorimetric quantification of linking in thermoreversible nanocrystal gel assemblies.

Kang, Jiho / Valenzuela, Stephanie A / Lin, Emily Y / Dominguez, Manuel N / Sherman, Zachary M / Truskett, Thomas M / Anslyn, Eric V / Milliron, Delia J

Science advances

2022 Volume 8, Issue 7, Page(s) eabm7364

Abstract: Nanocrystal gels can be responsive, tunable materials, but designing their structure and properties is challenging. By using reversibly bonded molecular linkers, gelation can be realized under conditions predicted by thermodynamics. However, simulations ... ...

Abstract	Nanocrystal gels can be responsive, tunable materials, but designing their structure and properties is challenging. By using reversibly bonded molecular linkers, gelation can be realized under conditions predicted by thermodynamics. However, simulations have offered the only microscopic insights, with no experimental means to monitor linking leading to gelation. We introduce a metal coordination linkage with a distinct optical signature allowing us to quantify linking in situ and establish structural and thermodynamic bases for assembly. Because of coupling between linked indium tin oxide nanocrystals, their infrared absorption shifts abruptly at a chemically tunable gelation temperature. We quantify bonding spectroscopically and use molecular simulation to understand temperature-dependent bonding motifs, revealing that gel formation is governed by reaching a critical number of effective links that extend the nanocrystal network. Microscopic insights from our colorimetric linking chemistry enable switchable gels based on thermodynamic principles, opening the door to rational design of programmable nanocrystal networks.
Language	English
Publishing date	2022-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abm7364
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Article ; Online: The RNA-binding protein SART3 promotes miR-34a biogenesis and G

Sherman, Emily J / Mitchell, Dylan C / Garner, Amanda L

The Journal of biological chemistry

2019 Volume 294, Issue 46, Page(s) 17188–17196

Abstract: MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of most biological processes. Global miRNA biogenesis is altered in many cancers, and RNA-binding proteins play a role in miRNA biogenesis, presenting a promising ... ...

Abstract	MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of most biological processes. Global miRNA biogenesis is altered in many cancers, and RNA-binding proteins play a role in miRNA biogenesis, presenting a promising avenue for targeting miRNA dysregulation in diseases. miR-34a exhibits tumor-suppressive activities by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor BCL-2, among other regulatory pathways such as Wnt, TGF-β, and Notch signaling. Many cancers exhibit down-regulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth
MeSH term(s)	Antigens, Neoplasm/genetics ; Apoptosis/genetics ; Cell Cycle Checkpoints/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; MicroRNAs/genetics ; Neoplasm Proteins/genetics ; Protein Binding/genetics ; Proteomics/methods ; RNA-Binding Proteins/genetics ; Spliceosomes/genetics
Chemical Substances	Antigens, Neoplasm ; MIRN34 microRNA, human ; MicroRNAs ; Neoplasm Proteins ; RNA-Binding Proteins ; SART3 protein, human ; mirnlet7 microRNA, human
Language	English
Publishing date	2019-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.AC119.010419
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Article ; Online: Click Chemistry-Mediated Complementation Assay for RNA-Protein Interactions.

Sherman, Emily J / Lorenz, Daniel A / Garner, Amanda L

ACS combinatorial science

2019 Volume 21, Issue 7, Page(s) 522–527

Abstract: Click chemistry-based assays are a growing class of biochemical assay for facilitating the discovery of modulators of important biological processes. To date, most have relied on the use of immobilized biomolecules, which increases the cost of the assay ... ...

Abstract	Click chemistry-based assays are a growing class of biochemical assay for facilitating the discovery of modulators of important biological processes. To date, most have relied on the use of immobilized biomolecules, which increases the cost of the assay and decreases throughput because of the necessary washing steps. To overcome these challenges, we have developed a click chemistry-mediated complementation assay that retains many of the advantages of the previous technology, including catalytic signal amplification for assay robustness and applicability to full-length biomolecules, but that can be performed in a homogeneous format. As demonstration of this methodology, we have developed a new high-throughput screening method for RNA-protein interactions using the interaction of Lin28 with the pre-microRNA, prelet-7, as a model.
MeSH term(s)	Click Chemistry ; Combinatorial Chemistry Techniques ; Humans ; MicroRNAs/chemistry ; Molecular Structure ; Proteins/chemistry
Chemical Substances	MicroRNAs ; Proteins
Language	English
Publishing date	2019-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2156-8944
ISSN (online)	2156-8944
DOI	10.1021/acscombsci.9b00071
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