Investigating Smooth Muscle Myosin Dynamics and Assembly in Physiology and Pathology

Vascular smooth muscle cells (SMCs) surround many blood vessels throughout the body,where they dynamically alter vessel diameter to regulate blood pressure, provide structural integrity, and absorb shock on a beat-to-beat timescale. As smooth muscle function fails, profound vascular disease ensues, often with tragic results- even death. Smooth muscle myosin 2 (SM2) is the dominant motor protein that actuates contractility and allows SMCs to perform these vital functions. To function, SM2 monomers dynamically assemble into filaments, which upon SMC activation, associate with filamentous actin to drive contractility. Despite the critical contribution of SM2 to SMC function, foundational aspects of SM2 assembly and dynamics remain unexplored. To remedy this, we expressed EGFP-tagged SM2 in rat aortic smooth muscle cells (A7R5), which retained a cytosolic calcium and contractile response to the acetylcholine agonist carbachol. Using fluorescence recovery after photobleaching (FRAP), we observed rapid polymer exchange kinetics for SM2, more similar to non-muscle myosin 2 (NM2) than striated myosin 2s. Consistently, super-resolution imaging of SM2 and NM2 suggests they form filamentous co-polymers. Using a single cell filament assembly assay, we observed that the majority of SM2 is assembled in filaments at steady state, but that SMC activation with carbachol rapidly increases SM2 assembly levels. Carbachol also reduced polymer exchange kinetics, suggesting stabilization of filaments during SMC activation. This carbachol-induced increase in SM2 assembly and decrease in exchange kinetics closely parallels the cytosolic calcium and contractility kinetics. Furthermore, both dynamics and assembly of smooth muscle myosin were altered in pathological mutations associated with thoracic aortic aneurysm and dissection, suggesting regulation of dynamics and assembly are vital for smooth muscle function. Collectively, our data supports an updated model in which highly dynamic SM2 filaments assemble, are stabilized, and are activated to produce cell-scale contractile forces during SMC activation

Adult food security and the relationship with Adverse Childhood Experiences among residents of Appalachian North Carolina

Introduction: The Appalachian region has worse health outcomes than the remainder of the United States. These disparities are often linked to the underlying social and environmental determinants of health. Adverse childhood experiences (ACEs) are associated with poor health outcomes across the lifespan and have a significant impact on future social determinants as an adult, including food security status. Purpose: To explore the relationships between ACEs and food security among adults in the Appalachian counties of North Carolina and make comparisons with the rest of the state. Methods: Researchers used North Carolina’s 2012 Behavioral Risk Factor Surveillance System data; namely, the ACEs optional module which includes 11 items related to experiences respondents had before the age of 18 and a single item from the Social Context optional module to classify food security status. The sample was divided into three age categories (18-44, 45-64, and 65 and older) for statistical comparisons as well as by the indicator for Appalachian county. Using Stata 15, weighted logistic regression was utilized for examining relationships between variables. Results: ACEs were a statistically significant predictor of food insecurity across all respondents; each additional ACE was associated with a 13-21% increase in the odds of food insecurity, depending on age group. However, living in an Appalachian county was only a predictor for those age 45-64. Implications: These findings highlight the long-term effects of childhood experiences on food security generally, and in Appalachia particularly for middle-aged adults. Reducing ACEs could reduce food insecurity and improve health in the region

A qualitative evaluation of a Young Parents Program (YPP) - Parent and facilitator perspectives

Issue addressed: Young parents (\u3c25 years) have lower engagement with health and community services and are more likely to experience negative outcomes in the perinatal period compared to older parents. The aim of this study was to evaluate the short to medium‐term outcomes of the Young Parents Program (YPP), specifically designed to engage and support young parents, using responsive and codesign strategies in a community setting. Methods: A qualitative case study used data from interviews with participating parents (n = 20) and a focus group with YPP facilitators (n = 5). Results: The findings report on the following short to medium‐term YPP outcomes for parents and children. Young parents: are engaged in early parenting services that are welcoming, non-judgemental and holistic; build parenting skills, knowledge, confidence and are tuned into their infants’ needs; are empowered to codesign program activities to meet their parenting and non-parenting needs; have developed friendships and a social support network in their local community; and, are linked into community services and resources. Their children are cared for and stimulated with age‐appropriate interactions and play. Conclusion: Flexible, responsive and codesigned programs for young parents are effective means of connecting parents to services, social support networks and can provide learning opportunities, which enhance both child and parent attachment and development. So what? Qualitative evaluation provides an understanding of contextual factors – required to inform effective design and delivery of young parent community programs

Enrichment of dynamic chromosomal crosslinks drive phase separation of the nucleolus

Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms that underlie the sequestration of these sub-domains are largely unknown. Using a stochastic, bead-spring representation of chromatin in budding yeast, we find enrichment of protein-mediated, dynamic chromosomal cross-links recapitulates the segregation, morphology and self-interaction of the nucleolus. Rates and enrichment of dynamic crosslinking have profound consequences on domain morphology. Our model demonstrates the nucleolus is phase separated from other chromatin in the nucleus and predicts that multiple rDNA loci will form a single nucleolus independent of their location within the genome. Fluorescent labeling of budding yeast nucleoli with CDC14-GFP revealed that a split rDNA locus indeed forms a single nucleolus. We propose that nuclear sub-domains, such as the nucleolus, result from phase separations within the nucleus, which are driven by the enrichment of protein-mediated, dynamic chromosomal crosslinks

Expressions 2004-2006

https://openspace.dmacc.edu/expressions/1022/thumbnail.jp

Exile Vol. LVIII

Autumn Stiles: Biblical Brooklyn 5 Daniel Carlson: A Night Indoors 6 Moriah Ellenborgen: Cradle Drop 8 Nicco Pandolfi: Cardinality 10 Abby Current: Babies in the Snow 11 Maggie Reagan: Chimaera 13 Natalie Olivo: Treading Water 14 Julianne Hyer: Swatch Watch 21 Mimi Mendes de Leon: For Bosnia 23 A. Tangredi: How to Keep from Freezing 24 Autumn Stiles: Bodies and Bread 25 Christie Maillet: The Depth of a Song 26 Sam Heyman: First Kiss 27 Shawn Whites: Five Hundred Miles to Freedom 28 Ammon Hollister: Temptation 31 Caroline Clutterbuck: The Conspiracy in Your Smile 32 Nicco Pandolfi: Sore Subject 33 Meghan Callahan: Why Claire Left 34 Aaron Bennett: Ode to Arden 36 Daniel Carlson: Duty 37 Lindsey Clark: Snapshot 38 Steph Maniaci: Ode to an M&M 39 Abby Current: The Animal Bride 41 Julianne Hyer: Trees Pantoum 42 Ammon Hollister: Life Support 43 Maggie Reagan: Necropolis 44

Tractostorm 2 : Optimizing tractography dissection reproducibility with segmentation protocol dissemination

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White-matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time-consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in-depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel-based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.Peer reviewe

Learning about population-health through a community practice learning project: An evaluation study.

Increasing student nurse numbers requiring community placement learning opportunities has led to insufficient numbers of community nurses being available to support student nurses in the community. Although the study presented in the article is based in the UK this issue is reported widely in the literature across the globe. Universities in many countries have had to find innovative ways of providing community health learning opportunities for student nurses. This article reports on how one university in the UK has approached this challenge through students engaging in a population-based study in the community through group work. A research study was undertaken into this innovation which found that the student nurses engaged well with the project and with their groups and undertaking the project had positive value and impact on them and their understanding of population-health. Issues that arose for them largely focused on unequal participation in the group work by some with many participants perceiving that they had done more work on the group project and presentation than others in their group. However, working in this way was perceived to be a good learning experience for the majority of participants