Achieving Evaluation Influence Through Elaboration Likelihood Model-informed Evaluation Product Designs

The ultimate purpose of evaluation is social betterment, which is achieved through evaluation influence. Progress has been made in defining the mechanisms of evaluation influence (Mark & Henry, 2004); however, little research has explored how the design of evaluation products trigger these mechanisms. Sister fields such as persuasion psychology can provide guidance to fill this gap. The Elaboration Likelihood Model, a dual-processing model of persuasion, provides insights into how persuasive information is processed and how this processing impacts attitude formation and behavioral intention (Petty & Cacioppo, 1986). By translating the principles of the Elaboration Likelihood Model, this research explores how various data presentation conventions -- minimalist, embellished, and interactive -- impact evaluation influence. In the first phase of this research, minimalist and embellished data visualization conventions did not result in differences in participant experience of the visualization nor different interpretation or attitudinal outcomes; however, motivation to elaborate significantly impacted both participant experiences and outcomes. Additionally, engagement with the data visualization played a role in how participants processed the evaluation findings, with highly engaged individuals basing their evaluand-specific attitudes on the strength of the evaluation findings. The second phase of this research demonstrated no significant differences in attitude strength and donation behaviors between minimalist and embellished data visualization. Instead, donation behaviors were driven by attitudes formed after reading the evaluation findings and motivation to elaborate. The final experiment found that interactive data presentations promoted elaboration and the formation of attitudes based on the strength of the evaluation findings. Additionally, significant differences in attitude persistence and behavioral intent were found based on the strength of evaluation findings; behavioral intent was additionally impacted by motivation to elaborate and engagement with the data presentation. Finally, donation behaviors were driven by motivation to elaborate, engagement with the data presentation, and evaluand-specific attitudes formed after reading the evaluation findings. The results of this research demonstrate that the design of evaluation products and audience characteristics such as motivation to elaborate can be factors impacting evaluation influence. Based on these findings, evaluation practitioners can promote evaluation influence by seeking out opportunities to design products that increase audience involvement to support elaboration processes. The current research also identifies both risks to and opportunities for increased evaluation influence based on the audiences\u27 level of motivation to elaborate, which provide guidance to evaluation practitioners seeking to maximize their evaluation\u27s impact. More broadly, this research advances new directions for research on evaluation influence by providing empirical evidence for influence pathways, for data visualization research by demonstrating the importance of motivation to elaborate to visualization experience and outcomes, and for research on the application of Elaboration Likelihood Model principles within the context of evaluation

Three pregnancies in a Marfan syndrome patient after a mitral and tricuspid valve surgery

Marfan syndrome is an autosomal dominant disorder of connective tissue with up to 25% of cases related to a spontaneous mutation. It has been associated with perinatal loss, preterm labor, and, potentially, a rupture of the maternal aortic arch. We present a case of a woman diagnosed with Marfan syndrome after a miscarriage of her first pregnancy. At the time of diagnosis she had mild aortic bulb dilation and insufficiency of the mitral and tricuspid valves. She underwent cardiosurgical correction, after which she had two uneventful pregnancies. This case suggests that preconceptional correction of valve defects in women with Marfan syndrome may decrease the risk of cardiac decompensation during future pregnancies. Additionally, close clinical follow up and the appropriate use of beta-adrenergic blockade may decrease the risk of aortic rupture, a significant risk factor for mortality in pregnant women

Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice

In humans, short-term supplementation with nitrate is hypotensive and inhibits platelet aggregation via an nitric oxide (NO)-dependent mechanism. In the present work, we analyzed whether short-term treatment with nitrate induces antithrombotic effects in rats and mice. Arterial thrombosis was evoked electrically in a rat model in which renovascular hypertension was induced by partial ligation of the left renal artery. In mice expressing green fluorescent protein, laser-induced thrombosis was analyzed intravitally by using confocal microscope. Sodium nitrate (NaNO(3)) or sodium nitrite (NaNO(2)) was administered orally at a dose of 0.17 mmol/kg, twice per day for 3 days. Short-term nitrate treatment did not modify thrombus formation in either rats or mice, while nitrite administration led to pronounced antithrombotic activity. In hypertensive rats, nitrite treatment resulted in a significant decrease in thrombus weight (0.50 ± 0.08 mg vs. VEH 0.96 ± 0.09 mg; p < 0.01). In addition, nitrite inhibited ex vivo platelet aggregation and thromboxane B(2) (TxB(2)) generation and prolonged prothrombin time. These effects were accompanied by significant increases in blood NOHb concentration and plasma nitrite concentration. In contrast, nitrate did not affect ex vivo platelet aggregation or prothrombin time and led to only slightly elevated nitrite plasma concentration. In mice, nitrate was also ineffective, while nitrite led to decreased platelet accumulation in the area of laser-induced endothelial injury. In conclusion, although nitrite induced profound NO-dependent antithrombotic effects in vivo, conversion of nitrates to nitrite in rats and mice over short-term 3-day treatment was not sufficient to elicit NO-dependent antiplatelet or antithrombotic effects

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM

OBJECTIVE: Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. APPROACH AND RESULTS: Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation. CONCLUSIONS: We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation

A reversible light- and genotype-dependent acquired thermotolerance response protects the potato plant from damage due to excessive temperature

A powerful acquired thermotolerance response in potato was demonstrated and characterised in detail, showing the time course required for tolerance, the reversibility of the process and requirement for light. Potato is particularly vulnerable to increased temperature, considered to be the most important uncontrollable factor affecting growth and yield of this globally significant crop. Here, we describe an acquired thermotolerance response in potato, whereby treatment at a mildly elevated temperature primes the plant for more severe heat stress. We define the time course for acquiring thermotolerance and demonstrate that light is essential for the process. In all four commercial tetraploid cultivars that were tested, acquisition of thermotolerance by priming was required for tolerance at elevated temperature. Accessions from several wild-type species and diploid genotypes did not require priming for heat tolerance under the test conditions employed, suggesting that useful variation for this trait exists. Physiological, transcriptomic and metabolomic approaches were employed to elucidate potential mechanisms that underpin the acquisition of heat tolerance. This analysis indicated a role for cell wall modification, auxin and ethylene signalling, and chromatin remodelling in acclimatory priming resulting in reduced metabolic perturbation and delayed stress responses in acclimated plants following transfer to 40 °C

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis is Associated with Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM

Objective-Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. Approach and Results-Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitationsequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation. Conclusions-We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation

Novel markers for smooth muscle cell modulation in vascular injury and disease

Smooth muscle cells (SMCs) are major constituents of the vascular wall, indispensable for basic physiological functions of a healthy vessel, such as regulating vascular tone and blood pressure, but also critical during disease development. With remarkable plasticity, SMCs act as early responders to vessel wall injury, where by activating molecular mechanisms, including phenotypic modulation and transdifferentiation, they counteract detrimental stimuli and aim to restore vascular homeostasis. The nature of SMC response to injury constitutes a major determinant of cardiovascular pathologies, including atherosclerosis, restenosis and aortic aneurysms, however, despite extensive progress in understanding the biology behind SMC phenotypic modulation, its many aspects remain elusive. With this perspective, the presented thesis aimed to identify and comprehensively characterize novel molecular signatures demarcating SMC phenotypic modulation, with a particular focus on transcriptional and cytoskeletal regulation of various SMC transitions. Study I identified muscle contraction and actin cytoskeleton among the most downregulated pathways in atherosclerosis, while cytoskeleton-related leiomodin 1 (LMOD1), synaptopodin 2 (SYNPO2), PDZ And LIM Domain 7 (PDLIM7), phospholamban (PLN) and synemin (SYNM) emerged as the top molecular signatures repressed in atherosclerotic carotid plaques in comparison to control arteries. These genes positively correlated to classical contractility markers and showed abundant expression in SMCs in healthy arteries, but were largely absent from end-stage lesions. Subcellularly, the majority of the proteins localized to the SMC cytoskeleton and was significantly downregulated in response to atherosclerosis-relevant stimuli. Mechanistically, repression of PDLIM7 resulted in downregulation of SMC markers, and impaired cell spreading, but increased proliferation. Altogether, this study identifies a panel of novel sensitive SMC markers, which could serve as early indicators of SMC phenotypic modulation in vascular disease. Study II investigated the role of proprotein convertase subtilisin/kexin 6 (PCSK6), previously identified as one of the top molecules upregulated in human atherosclerotic plaques. PCSK6 localized to fibrous cap and neovessels in carotid lesions as well as to injuryinduced intimal hyperplasia, where it was expressed by proliferating smooth muscle alphaactin (SMA) + cells and shown to colocalize and co-interact with matrix metalloproteinases (MMPs) 2 and 14. Pcsk6-/- mice were characterized by the repression of SMC contractility markers and extracellular matrix (ECM) remodeling transcripts, displayed reduced intimal hyperplasia formation upon carotid ligation in vivo and impaired outgrowth of SMCs from aortic rings ex vivo, the latter two likely attributable to decreased MMP14 activity. In summary, this study establishes PCSK6 as a molecule of crucial importance for the SMC function in vascular remodeling. Study III focused on key molecular signatures in carotid plaques stratified by ultrasoundassessed echogenicity. BCL2 Associated Transcription Factor 1 (BCLAF1) emerged as a top molecule downregulated in relation to plaque echolucency, abundantly expressed in SMA+ SMCs in the normal arteries, strongly repressed early during atheroprogression, however restored in cluster of differentiation 68 (CD68) + cells in advanced lesions, where it was also shown to co-interact with pro-survival B-Cell CLL/Lymphoma 2 (BCL2). Repression of BCLAF1 resulted in suppression of SMC contractility markers, decreased cell viability, as well as partially prevented oxLDL-induced SMC transdifferentiation into macrophage-like cells by preserving higher MYH11 expression and reducing levels of CD36 and CD68 scavenger receptors. Overall, BCLAF1 emerged as a molecule indispensable for SMC survival and transdifferentiation into CD68+ macrophage-like cells. Study IV aimed to identify key transcription factors (TFs) in the control of SMC phenotype and function in human atherosclerosis. Forkhead Box C1 (FOXC1) emerged as a master upstream regulator of genes differentially expressed in carotid plaques compared to control arteries and in relation to patient symptomatology, involved in the regulation of cell cycle, response to T3 hormone and cell adhesion. It was abundantly expressed in SMA+ cells in the control arteries and plaques, strongly downregulated in early phases of vascular wall healing, with its expression gradually restored concomitantly with SMCs regaining their contractile properties. Silencing of FOXC1 resulted in significant repression of SMC contractility markers, increased migration and proliferation, as well as partially abolished T3-induced SMC phenotypic modulation. Altogether, these results provide compelling evidence for FOXC1 being an important TF in the control of SMC quiescence vs. activation, especially in response to T3. Collectively, by unraveling the intricacies of various aspects of SMC phenotypic modulation, this thesis contributes to a better understanding of molecular mechanisms underlying cardiovascular disease (CVD)