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Article ; Online: Relationships between eating disorder symptoms, muscle dysmorphia symptoms, and suicidal ideation: A random intercepts cross-lagged panel approach.

Grunewald, William / Troop-Gordon, Wendy / Smith, April R

The International journal of eating disorders

2022 Volume 55, Issue 12, Page(s) 1733–1743

Abstract: Objective: Eating disorder (ED) symptoms correlate with suicidality; yet the strength of these relationships in men is unclear. Muscle dysmorphia (MD) symptoms may reflect a more accurate index of body-related concerns for men, as they better target ... ...

Abstract	Objective: Eating disorder (ED) symptoms correlate with suicidality; yet the strength of these relationships in men is unclear. Muscle dysmorphia (MD) symptoms may reflect a more accurate index of body-related concerns for men, as they better target muscularity concerns typical of men. However, no studies have tested a model in which ED/MD symptoms and suicidality are simultaneously examined. We longitudinally tested whether ED/MD symptoms were related to suicidal ideation among a community sample of men. Methods: Men with MD symptoms (N = 272) were recruited to complete three surveys over 6 weeks. A random intercepts cross-lagged panel model tested predictive associations between ED/MD symptoms and suicidal ideation, while disaggregating between/within-person variance. Results: ED/MD symptoms were significantly associated with suicidal ideation at the between-subjects level (ED: b = .04; MD: b = .09) and showed significant within-wave covariances with suicidal ideation (ED: b = .02-.04; MD: b = .02-.05). Those who experienced increases in ED symptoms showed increased suicidal ideation at the next wave (b = .32). Those who experienced increases in suicidal ideation showed increases in MD symptoms at the next wave (b = .85). Discussion: Results highlight ED symptoms as a potential risk factor for suicidal ideation among men. Further, suicidal ideation predicted MD symptoms. ED symptoms may create intra- and interpersonal distress predicting suicidal ideation. Suicidal ideation may lead to muscle-building behaviors to cope with suicidal thoughts. Clinicians should assess for suicidal ideation among men at risk for MD/EDs, and for MD symptoms among those reporting suicidal ideation. Public significance: Eating disorder (ED) symptoms are related to suicidality, but these relationships are understudied among men. Since men report concerns surrounding muscularity, muscle dysmorphia (MD) may be a better ED index for this population. However, little research has investigated relationships between ED symptoms, MD symptoms, and suicidality among men. This study investigated relationships between ED/MD symptoms and suicidality among 272 men. Results may inform clinical assessment, treatment, and classification of MD.
MeSH term(s)	Humans ; Suicidal Ideation ; Muscles ; Feeding and Eating Disorders/diagnosis
Language	English
Publishing date	2022-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	603170-5
ISSN	1098-108X ; 0276-3478
ISSN (online)	1098-108X
ISSN	0276-3478
DOI	10.1002/eat.23819
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Article ; Online: The crystal structure of the human smacovirus 1 Rep domain.

Limón, Lidia K / Shi, Ke / Dao, Amy / Rugloski, Jacob / Tompkins, Kassidy J / Aihara, Hideki / Gordon, Wendy R / Evans, Robert L

Acta crystallographica. Section F, Structural biology communications

2023 Volume 79, Issue Pt 12, Page(s) 295–300

Abstract: Replication initiator proteins (Reps) from the HUH endonuclease family process specific single-stranded DNA sequences to initiate rolling-circle replication in viruses. Here, the first crystal structure of the apo state of a Rep domain from the ... ...

Abstract	Replication initiator proteins (Reps) from the HUH endonuclease family process specific single-stranded DNA sequences to initiate rolling-circle replication in viruses. Here, the first crystal structure of the apo state of a Rep domain from the smacovirus family is reported. The structure of the human smacovirus 1 Rep domain was obtained at 1.33 Å resolution and represents an expansion of the HUH endonuclease superfamily, allowing greater diversity in bioconjugation-tag applications.
MeSH term(s)	Humans ; Crystallography, X-Ray ; Endonucleases/chemistry ; DNA, Single-Stranded ; DNA, Viral/genetics
Chemical Substances	Endonucleases (EC 3.1.-) ; DNA, Single-Stranded ; DNA, Viral
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ISSN	2053-230X
ISSN (online)	2053-230X
DOI	10.1107/S2053230X23009536
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Article ; Online: Self-reported concussions in Canada: A cross-sectional study.

Champagne, André S / Yao, Xiaoquan / McFaull, Steven R / Saxena, Shikha / Gordon, Kevin R / Babul, Shelina / Thompson, Wendy

Health reports

2023 Volume 34, Issue 6, Page(s) 17–28

Abstract: Background: Traumatic brain injuries (TBIs) are a major public health concern impacting the lives of many Canadians. Among all TBIs, concussions are the most common. However, to date, the incidence of concussions among the Canadian population, has ... ...

Abstract	Background: Traumatic brain injuries (TBIs) are a major public health concern impacting the lives of many Canadians. Among all TBIs, concussions are the most common. However, to date, the incidence of concussions among the Canadian population, has remained unknown. To address this data surveillance gap, this study presents national estimates on the percentage of Canadians aged 12 years or older (excluding those living in the territories) who sustained one or more concussions in 2019. Data and methods: This study used data collected from the Traumatic Brain Injury Rapid Response (TBIRR) module of the 2020 Canadian Community Health Survey, a cross-sectional health survey. Descriptive statistics and logistic regressions were conducted to summarize the information in the TBIRR module. Results: This study found that approximately 1.6% of Canadians aged 12 years or older reported sustaining one or more concussions in 2019. Age was significantly associated with concussion incidence after controlling for sex and annual household income, and the locations and activities surrounding respondents' most serious concussions varied by age group. Over one-third of respondents sustained multiple concussions. Interpretation: The results suggest that certain populations, particularly younger individuals, may be more affected by concussions. While circumstances surrounding concussions vary by age group, the most important contributing factors were sports or physical activities among youth and falls among the adult population. Monitoring concussions among the national population is an important activity in injury surveillance, as it can help evaluate the efficacy of injury prevention intervention and better understand knowledge gaps and the burden of this injury.
MeSH term(s)	Adult ; Adolescent ; Humans ; Cross-Sectional Studies ; Athletic Injuries/epidemiology ; Self Report ; Canada/epidemiology ; Brain Concussion/epidemiology
Language	English
Publishing date	2023-06-21
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1057245-4
ISSN	1209-1367 ; 0840-6529
ISSN (online)	1209-1367
ISSN	0840-6529
DOI	10.25318/82-003-x202300600002-eng
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Article ; Online: Uso da mão de assistência e o desempenho bimanual no autocuidado de crianças com paralisia cerebral unilateral espástica.

Brandão, Marina B / Coster, Wendy J / Figueiredo, Priscilla R P / Amaral, Maíra F / Gordon, Andrew M / Mancini, Marisa C

Developmental medicine and child neurology

2022 Volume 65, Issue 3, Page(s) e1–e8

Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Journal Article
ZDB-ID	80369-8
ISSN	1469-8749 ; 0012-1622
ISSN (online)	1469-8749
ISSN	0012-1622
DOI	10.1111/dmcn.15368
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Article: Designing Efficient Enzymes: Eight Predicted Mutations Convert a Hydroxynitrile Lyase into an Efficient Esterase.

Casadevall, Guillem / Pierce, Colin / Guan, Bo / Iglesias-Fernandez, Javier / Lim, Huey-Yee / Greenberg, Lauren R / Walsh, Meghan E / Shi, Ke / Gordon, Wendy / Aihara, Hideki / Evans, Robert L / Kazlauskas, Romas / Osuna, Sílvia

bioRxiv : the preprint server for biology

2023

Abstract: Hydroxynitrile lyase from rubber tree ( ...

Abstract	Hydroxynitrile lyase from rubber tree (
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.23.554512
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Article ; Online: Enhanced Molecular Tension Sensor Based on Bioluminescence Resonance Energy Transfer (BRET).

Aird, Eric J / Tompkins, Kassidy J / Ramirez, Maria Paz / Gordon, Wendy R

ACS sensors

2020 Volume 5, Issue 1, Page(s) 34–39

Abstract: Molecular tension sensors measure piconewton forces experienced by individual proteins in the context of the cellular microenvironment. Current genetically encoded tension sensors use FRET to report on extension of a deformable peptide encoded in a ... ...

Abstract	Molecular tension sensors measure piconewton forces experienced by individual proteins in the context of the cellular microenvironment. Current genetically encoded tension sensors use FRET to report on extension of a deformable peptide encoded in a cellular protein of interest. Here, we present the development and characterization of a new type of molecular tension sensor based on bioluminescence resonance energy transfer (BRET), which exhibits more desirable spectral properties and an enhanced dynamic range compared to other molecular tension sensors. Moreover, it avoids many disadvantages of FRET measurements in cells, including autofluorescence, photobleaching, and corrections of direct acceptor excitation. We benchmark the sensor by inserting it into the canonical mechanosensing focal adhesion protein vinculin, observing highly resolved gradients of tensional changes across focal adhesions. We anticipate that the BRET tension sensor will expand the toolkit available to study mechanotransduction at a molecular level and allow potential extension to an in vivo context.
MeSH term(s)	Biosensing Techniques/methods ; Fluorescence Resonance Energy Transfer/methods ; Humans
Language	English
Publishing date	2020-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.9b00796
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Article ; Online: A toolkit for studying cell surface shedding of diverse transmembrane receptors.

Hayward, Amanda N / Aird, Eric J / Gordon, Wendy R

eLife

2019 Volume 8

Abstract: Proteolysis of transmembrane receptors is a critical cellular communication mechanism dysregulated in disease, yet decoding proteolytic regulation mechanisms of hundreds of shed receptors is hindered by difficulties controlling stimuli and unknown fates ... ...

Abstract	Proteolysis of transmembrane receptors is a critical cellular communication mechanism dysregulated in disease, yet decoding proteolytic regulation mechanisms of hundreds of shed receptors is hindered by difficulties controlling stimuli and unknown fates of cleavage products. Notch proteolytic regulation is a notable exception, where intercellular forces drive exposure of a cryptic protease site within a juxtamembrane proteolytic switch domain to activate transcriptional programs. We created a Synthetic Notch Assay for Proteolytic Switches (SNAPS) that exploits the modularity and unequivocal input/response of Notch proteolysis to screen surface receptors for other putative proteolytic switches. We identify several new proteolytic switches among receptors with structural homology to Notch. We demonstrate SNAPS can detect shedding in chimeras of diverse cell surface receptors, leading to new, testable hypotheses. Finally, we establish the assay can be used to measure modulation of proteolysis by potential therapeutics and offer new mechanistic insights into how DECMA-1 disrupts cell adhesion.
MeSH term(s)	Biological Assay ; Cadherins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Dystroglycans/metabolism ; Humans ; Matrix Metalloproteinases/metabolism ; Protein Domains ; Proteolysis ; Receptors, Cell Surface/chemistry ; Receptors, Cell Surface/metabolism ; Trastuzumab/metabolism
Chemical Substances	Cadherins ; Receptors, Cell Surface ; Dystroglycans (146888-27-9) ; Matrix Metalloproteinases (EC 3.4.24.-) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2019-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.46983
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Article ; Online: Watson-Crick Base-Pairing Requirements for ssDNA Recognition and Processing in Replication-Initiating HUH Endonucleases.

Smiley, Adam T / Tompkins, Kassidy J / Pawlak, Matthew R / Krueger, August J / Evans, Robert L / Shi, Ke / Aihara, Hideki / Gordon, Wendy R

mBio

2022 Volume 14, Issue 1, Page(s) e0258722

Abstract: Replication-initiating HUH endonucleases (Reps) are sequence-specific nucleases that cleave and rejoin single-stranded DNA (ssDNA) during rolling-circle replication. These functions are mediated by covalent linkage of the Rep to its substrate post ... ...

Abstract	Replication-initiating HUH endonucleases (Reps) are sequence-specific nucleases that cleave and rejoin single-stranded DNA (ssDNA) during rolling-circle replication. These functions are mediated by covalent linkage of the Rep to its substrate post cleavage. Here, we describe the structures of the endonuclease domain from the Muscovy duck circovirus Rep in complex with its cognate ssDNA 10-mer with and without manganese in the active site. Structural and functional analyses demonstrate that divalent cations play both catalytic and structural roles in Reps by polarizing and positioning their substrate. Further structural comparisons highlight the importance of an intramolecular substrate Watson-Crick (WC) base pairing between the -4 and +1 positions. Subsequent kinetic and functional analyses demonstrate a functional dependency on WC base pairing between these positions regardless of the pair's identity (i.e., A·T, T·A, G·C, or C·G), highlighting a structural specificity for substrate interaction. Finally, considering how well WC swaps were tolerated
MeSH term(s)	Humans ; Base Pairing ; DNA, Single-Stranded/genetics ; Endonucleases/metabolism ; Circovirus/genetics
Chemical Substances	DNA, Single-Stranded ; Endonucleases (EC 3.1.-)
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02587-22
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Article ; Online: Assisting hand use and self-care bimanual performance of children with unilateral spastic cerebral palsy.

Brandão, Marina B / Coster, Wendy J / Figueiredo, Priscilla R P / Amaral, Maíra F / Gordon, Andrew M / Mancini, Marisa C

Developmental medicine and child neurology

2022 Volume 65, Issue 3, Page(s) 385–392

Abstract: Aim: To examine the relationship between assisting hand use in bimanual activities and children's self-care activities and task performance.: Method: We retrospectively analysed daily functioning (Pediatric Evaluation of Disability Inventory [PEDI]) ... ...

Abstract	Aim: To examine the relationship between assisting hand use in bimanual activities and children's self-care activities and task performance. Method: We retrospectively analysed daily functioning (Pediatric Evaluation of Disability Inventory [PEDI]) and bimanual performance (Assisting Hand Assessment [AHA]) data from the assessment of 112 children (mean age: 8 years 10 months [SD 2 years 1 month], range 3 years 7 months-17 years 4 months; 66 males, 46 females) with unilateral spastic cerebral palsy (CP). We used Rasch analysis to examine the relationship between individual item scores from the AHA and the self-care items (functional skills, caregiver assistance) from the PEDI. Results: Most self-care functional skills and caregiver-assisted tasks were located on the middle of the unidimensional continuum. These items showed similar levels of difficulty as the items from the AHA related to the effective coordination of two hands, appropriate pace, and use of the assisting hand to stabilize and release objects, as well as variations in arm movements. Interpretation: The distribution of the PEDI self-care and AHA items along the unidimensional continuum illustrates the relationship between assisting hand use and self-care bimanual performance. Interpretation of the items' locations on the hierarchical unidimensional continuum may be helpful to therapists' clinical reasoning and suggest intervention goals to improve the hand function and daily functioning of children with unilateral spastic CP. Such an application needs further investigation.
MeSH term(s)	Male ; Female ; Child ; Humans ; Infant ; Retrospective Studies ; Cerebral Palsy ; Self Care ; Motor Skills ; Hand
Language	English
Publishing date	2022-07-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80369-8
ISSN	1469-8749 ; 0012-1622
ISSN (online)	1469-8749
ISSN	0012-1622
DOI	10.1111/dmcn.15362
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Article ; Online: RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes.

Pawlak, Matthew R / Smiley, Adam T / Ramirez, Maria Paz / Kelly, Marcus D / Shamsan, Ghaidan A / Anderson, Sarah M / Smeester, Branden A / Largaespada, David A / Odde, David J / Gordon, Wendy R

Nature communications

2023 Volume 14, Issue 1, Page(s) 2468

Abstract: Mechanical forces drive critical cellular processes that are reflected in mechanical phenotypes, or mechanotypes, of cells and their microenvironment. We present here "Rupture And Deliver" Tension Gauge Tethers (RAD-TGTs) in which flow cytometry is used ... ...

Abstract	Mechanical forces drive critical cellular processes that are reflected in mechanical phenotypes, or mechanotypes, of cells and their microenvironment. We present here "Rupture And Deliver" Tension Gauge Tethers (RAD-TGTs) in which flow cytometry is used to record the mechanical history of thousands of cells exerting forces on their surroundings via their propensity to rupture immobilized DNA duplex tension probes. We demonstrate that RAD-TGTs recapitulate prior DNA tension probe studies while also yielding a gain of fluorescence in the force-generating cell that is detectable by flow cytometry. Furthermore, the rupture propensity is altered following disruption of the cytoskeleton using drugs or CRISPR-knockout of mechanosensing proteins. Importantly, RAD-TGTs can differentiate distinct mechanotypes among mixed populations of cells. We also establish oligo rupture and delivery can be measured via DNA sequencing. RAD-TGTs provide a facile and powerful assay to enable high-throughput mechanotype profiling, which could find various applications, for example, in combination with CRISPR screens and -omics analysis.
MeSH term(s)	DNA Probes ; Mechanical Phenomena ; Proteins ; Cell Physiological Phenomena ; DNA
Chemical Substances	DNA Probes ; Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2023-04-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38157-6
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