Pediatric Giant Right Atrial Aneurysm: A Case Series and Review of the Literature

Giant right atrial aneurysm is a rare form of congenital heart disease with a wide spectrum of clinical presentation varying from asymptomatic patients to those with refractory atrial arrhythmias or severe airway obstruction. Diagnosis is often confused with other causes of right atrial dilation such as E bstein disease. Because of its rare occurrence and variable clinical presentation, inconsistencies in medical and surgical management strategies exist between centers. We present five cases of giant right atrial aneurysm managed at our institution and discuss the clinical presentation, diagnostic challenges, and medical and surgical management.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107528/1/chd12079.pd

Studies of G Protein-Coupled Receptor Stability and Dimerization Using Novel Fluorescence and Crosslinking Approaches

G protein-coupled receptors (GPCRs) comprise a large family of related seventransmembrane- helical membrane proteins that bind to specific extracellular ligands, such as hormones or neuromodulators. The active receptor-ligand complex then engages with a heterotrimeric G protein on the cytoplasmic surface of the plasma membrane to facilitate a change in the concentration of an intracellular second messenger, such as cAMP. A number of non-canonical signaling pathways, such as β-arrestin-mediated signaling, also exist for many, if not all, GPCRs. Receptor signaling is attenuated by phosphorylation and receptor internalization. Recent advances in structural studies of GPCRs have revealed high-resolution structures of both inactive and active receptors in complex with various ligands. Endogenous ligands, drugs and the membrane environment, and even oligomerization can affect receptor signaling efficacy, but the mechanistic details underlying these allosteric effects are poorly characterized. To study allosterism of a ligand-receptor complex in a bilayer requires at least partial enrichment or isolation of the basic signaling unit. Many studies have employed biochemical purification and reconstitution strategies, but GPCRs are inherently unstable when extracted from native membranes so conditions must be carefully selected to preserve receptor integrity. To monitor the functional state of GPCRs during purification and reconstitution, a novel homogeneous time-resolved fluorescence resonance energy transfer (FRET)-based analytical assay was developed. To enable the assay, a novel bioconjugation method was invented to prepare microgram quantities of monoclonal antibodies labeled with long-lived lanthanide fluorophores. As a proof-of-concept, the folding and stability of human C-C chemokine receptor 5 (CCR5), the primary coreceptor for HIV-1 cellular entry, was studied. The assay enabled high-throughput detection of femtomole quantities of CCR5. Thermal denaturation measurements demonstrated that small molecule antagonists substantially stabilize CCR5 and also revealed that the ligands induce distinct receptor conformations, consistent with the hypothesis that GPCRs access numerous conformations during signal transduction rather than operating as a binary active-inactive switch. In addition, high-throughput stability screens led directly to the identification of CCR5 mutants that should be sufficiently stable for crystallization and lead to a high-resolution structure of CCR5, which would significantly advance understanding of the structural basis of HIV entry. The FRETbased assay was also applied to devise and optimize a protocol to incorporate CCR5 into an artificial membrane scaffold called nanoscale apolipoprotein bound bilayers (NABBs). CCR5 was shown to retain proper folding in NABBs and proof-of-concept fluorescence correlation spectroscopy (FCS) experiments were carried out to characterize these structures. Novel FCS standard reagents were developed to facilitate these measurements. The biochemical and analytical approaches reported may be adapted to prepare stable, functional samples of other GPCRs for structural and dynamic studies of receptor allostery. GPCRs are known to form dimers and higher-order oligomers, and despite a growing body of evidence that these complexes are functionally important, the structural basis of receptor-receptor interactions remains unknown. To address this problem, a potential dimerization interface of the prototypical GPCR, rhodopsin, was analyzed using a proteomics approach involving chemical crosslinking and liquid chromatography-mass spectrometry. The strategy was devised so that rhodopsin could be probed in the unique native environment of the rod cell disk membrane. Crosslinking results supported a model of rhodopsin dimerization involving contacts in transmembrane helix 1 and an amphipathic cytoplasmic helix at the carboxyl-terminal tail of the receptor. This novel interface is postulated to be relevant for understanding GPCR oligomerization in general

In-field and Greenhouse Assessments of a Selection of Preemergent Herbicides on Newly Planted Blackberries

This field trial assesses some of the preemergence herbicide options available to growers and their effect on newly transplanted blackberries (Rubus L. subgenus Rubus Watson). Weed control has recently been surveyed as a top priority for blackberry growers; however, limited preemergence herbicides are registered for new blackberry plantings. Weed control is an ongoing component of blackberry production and with few in-season postemergence herbicide options available, growers rely on preemergence herbicides to maintain clean fields. The preemergent herbicides assessed in this trial were chosen with the intention to broaden the chemical control options available to growers in new plantings. A two-year field trial was initiated in 2021 and conducted at two locations: Milo J. Shult Research and Extension Center in Fayetteville, AR (36.09 ºN, 94.17 ºW) and the University of Arkansas Fruit Research Station in Clarksville, AR (35.53 ºN, 93.40 ºW). Seven treatments consisting of six preemergence herbicides (mesotrione, flumioxazin, oryzalin, S-metolachlor, pendimethalin, and napropamide) and one hand-weeded check were applied to field plots of newly transplanted tissue culture propagated blackberry plugs (var. ‘Ouachita’). Preemergence herbicide treatments were reapplied to the same plots in 2022. Data were collected on visual injury, plant height, leaf chlorophyll content, and green coverage of blackberry canopies and of bare ground portions of each plot. Yield data were collected in the second year, and fruit were analyzed for soluble solids content (°Brix), pH, and average berry weight. In the first year mesotrione and flumioxazin treatments caused the most injury to the primocanes. Injury by flumioxazin was not detectable at the final rating of the first year, but injury by mesotrione was high 84 days after treatment (DAT). Napropamide, S-metolachlor, oryzalin, and pendimethalin did not cause injury over 6% throughout the 2021 season. In the second year (2022) no damage was incurred by any treatments, from the treated or the non-chemical weed-free (NCWF) check. The mesotrione treatment affected plant height the most in 2021 at the end of the season compared to the NCWF check. In 2022 plant height was not assessed. Yield measurements taken in 2022 exhibited no significant differences in response to preemergence herbicide treatments. A greenhouse experiment was conducted to investigate the effects of a broad selection of preemergence herbicides at two rates. This screening was initiated August 2021 and repeated March 2022 in Fayetteville, AR in a horticultural greenhouse at the Milo J. Shult Research and Extension Center. Tissue cultured ‘Ouachita’ blackberry plugs were transplanted into utility pots that were treated with a preemergence herbicide treatment. Twenty-five treatments in total consisted of twelve preemergence herbicides at 1× and 2× rates and one untreated control. Data were collected on plant height, visual injury ratings, internode length, leaf chlorophyll content, and destructive harvest including leaf count, leaf dry biomass, specific leaf area (SLA), and leaf area to dry matter ratio (LADMR). Halosulfuron, rimsulfuron, and mesotrione treatments showed progressively increasing visual injury from 7 days after treatment (DAT) until 42 DAT. Flumioxazin, napropamide, S-metolachlor, and pendimethalin treatments exhibited similar responses to the untreated control regarding height and visual injury and may be acceptable for use in young blackberry weed management programs. Data obtained from this screening characterized the physiological response of new blackberries treated with these preemergence herbicides. Both trials demonstrated the deleterious effects of mesotrione on young plants and why it is not recommended for use in first year plantings. Both trials demonstrated the validity of the 24(c) labeling of S-metolachlor. These findings validate many of the regional recommendations and provide new evidence to consider expanding registration and labeled usage requirements for select preemergence herbicides. This knowledge and further field investigation have the potential to lead to more informed IPM strategies

Supporting First-Generation College Students Experiencing Imposter Syndrome

This project explores the relationship between imposter syndrome and academic performance in first-generation college students (FGCS), proposing a peer mentorship program as an intervention. Grounded in Kolontari et al.’s (2023) sponsorship model and Stoller’s (2021) integration of Chickering’s (1969) and Sanford’s (1966) theories, the program focuses on mentor selection, training, structured activities, and ongoing support to build self-efficacy and a sense of belonging. A key component of this solution is the implementation of horizontal peer mentorship, which encourages reciprocal, collaborative relationships between mentors and mentees. FGCS mentors are trained to address imposter syndrome firsthand, with activities like self-affirmation exercises and peer reflection journals designed to boost confidence and emotional expression. A mixed-methods evaluation will assess changes in self-efficacy, imposter syndrome, and academic outcomes through qualitative feedback. This project provides a research-based approach to reducing imposter syndrome and improving academic success for FGCS while highlighting future research opportunities on long-term mentorship outcomes and the development of equity-centered student support strategies across diverse institutions

Development of Standardized S Curves for the Evaluation of Major Department of Defense Purchases

The increasing cost of Department of Defense acquisitions combined with the shrinking Defense budget puts a premium on continuing the funding of only those programs that are practical and affordable. This emphasizes a need for good methods of monitoring the progress of programs. Current methods of controlling and evaluating cost performance are limited. It is our belief that the generation of S-curves using current Cost and Schedule Control Systems Criteria (C/SCSC) data will provide a mathematical and/or graphical approach to assist in the control of program costs. This thesis attempted to plot the percentage of time for a contract\u27s completion against the percentage of actual cost spent during that period. Each contract was separated into a sub-category, averaged and then plotted. This developed a signature curve for categories of contracts

Molecular heterogeneity in human stroke - What can we learn from the peripheral blood transcriptome?

Stroke is a multifaceted disease with genetic and environmental components like diet and lifestyle. The central nervous and immune systems display complex interactions, with the peripheral immune response participating in brain injury and repair mechanisms following stroke. The bidirectional communication between the injured brain and peripheral blood presents an opportunity to investigate the molecular changes in the latter. There is substantial heterogeneity in stroke pathogenesis, pathophysiology, comorbidities, and response to treatment and outcome. This is captured and underscored by heterogeneity in the peripheral blood transcriptome. The current review highlights the role of the human peripheral blood transcriptome architecture for molecular phenotyping of different stroke etiologies and comorbidities, and for identifying underlying molecular correlates with clinically important variables and outcomes. Specific transcriptome features can potentially provide targets for clinical translation and for prioritizing genes and pathways for evaluation in experimental models. We also propose an approach to study the patient-specific transcriptional architecture and uncover the combinatorial heterogeneity in altered pathways in stroke patients that can also guide the search for treatment and prevention targets. Deciphering the molecular heterogeneity of stroke in a tissue that can be easily accessed and monitored, such as peripheral blood, may improve clinical trial success

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention