Biology subjects

Johnson, E. G.

Publications and source records attributed to Johnson, E. G..

4 recordsLinked to original sources

bioRxiv2026

A Large Animal Model of Heritable Pulmonary Arterial Hypertension UsingGene-edited BMPR2 Sheep

Pulmonary Arterial Hypertension (PAH) is a rare vascular disorder characterized by elevated pressure in pulmonary arteries, eventually leading to right ventricular failure. Approximately 50% of pediatric disease and 20% of adult disease can be linked to a genetic mutation, with nearly 70% of these cases involving mutations in the bone morphogenetic protein receptor type 2 (BMPR2) locus. Investigations using rodent models have made significant advances in our understanding of BMPR2 signaling; however, limited data exist regarding the onset and course of PAH, and etiologies for phenotypic expression in these patients remain unknown. In this work, we describe the development of a novel ovine model of heritable PAH. Because homozygous disruption of BMPR2 is embryonic lethal, we developed heterozygous BMPR2 sheep by using a PAM-disrupting synonymous single stranded oligodeoxyribonucleotide alongside a single guide RNA and Cas9 mediated gene editing strategy. The resulting BMPR2(+/-) lambs demonstrated cardiac and pulmonary vascular pathology that are consistent with BMPR2 mutation-driven PAH observed in humans. Given the genetic and physiological similarities of BMPR2(+/-)sheep to humans with heritable PAH, this large animal model will serve as a vital platform for mechanistic molecular studies and will provide a much-needed pre-clinical model for extensive treatment evaluations.

molecular biology↗

bioRxiv2025

Pulmonary Vascular Endothelial Dysfunction is Induced by Non-Pulsatile Pulmonary Blood Flow in an Ovine Classic Glenn Model

Structured AbstractO_ST_ABSBackgroundC_ST_ABSPulmonary vascular disease (PVD) in patients with single ventricular heart disease following the partial cavalpulmonary connection (Glenn) is a significant source of morbidity. However, the etiology of pulmonary vascular endothelial cell (EC) dysfunction, an established precursor to PVD, is incompletely understood but may involve abnormal blood flow patterns, hypoxemia, and polycythemia. HypothesisUtilizing an ovine Glenn model, we hypothesized that non-pulsatile pulmonary blood flow (PBF) induces pulmonary vascular EC dysfunction, independent of hypoxemia or polycythemia. MethodsSeven lambs (6-8 weeks old) underwent a Glenn procedure. Eight weeks later, Glenn and age-matched controls were studied. The response to the endothelium-dependent vasodilator acetylcholine (Ach) was determined in isolated pulmonary arteries (PA). Nitric oxide (NO) and endothelin-1 (ET-1) signaling was determined in right lung tissues. Indices of cell proliferation, angiogenesis, and apoptosis were determined in PA endothelial cells (PAECs). Comparisons were made by unpaired t-test and ANOVA. ResultsThere were no differences in age, hemoglobin, or oxygen saturation between groups. Mean PA pressure and left PA flow were higher, and right lung blood flow was lower in Glenn lambs compared to controls (p<0.05). All other baseline hemodynamics were similar. Glenn PAs had impaired relaxation to Ach. Glenn lung NO metabolite levels (NOx) and eNOS protein were lower, and ET-1 levels and prepro-ET-1 protein were higher than controls (p<0.05). Glenn PAECs had higher rates of proliferation and angiogenesis, and decreased apoptosis (p < 0.05). ConclusionsThe initiation of non-pulsatile PBF following the Glenn induces early EC dysfunction independent of hypoxemia and polycythemia.

physiology↗

bioRxiv2020

Total mercury concentrations in invasive lionfish (Pterois volitans/miles) from the Atlantic coast of Florida

ABSTRACTInvasive lionfish (Pterois volitans/miles) pose a serious threat to marine ecosystems throughout the western Atlantic Ocean and Caribbean Sea. The development of a fishery for lionfish has been proposed as a strategy for controlling populations; however, there is concern about consumption of this species by humans due to its high trophic position and potential for bioaccumulation of mercury. We analyzed total mercury (THg) in tissues of lionfish from two locations on the east coast of Florida. THg in lionfish increased with size and differed by location and sex. THg was highest in muscle tissue and was strongly positively correlated among tissues. THg in lionfish was lower than other commonly consumed marine fishes, and falls into Florida’s least restrictive advisory level. Consumption of lionfish poses a low risk and concerns over mercury bioaccumulation should not present a significant barrier to lionfish harvest.View Full Text

pharmacology and toxicology↗

bioRxiv2019

Changes in anterior and posterior hippocampus differentially predict item-space, item-time, and item-item memory improvement

Relational memory requires the hippocampus, but whether distinct hippocampal mechanisms along the anterior-posterior axis are required for different types of relations is debated. We investigated the contribution of structural changes in hippocampal head, body, and tail subregions to the capacity to remember item-space, item-time, and item-item relations. Memory for each relation and volumes of hippocampal subregions were assessed longitudinally in 171 participants across 3 time points (Mage at T1= 9.45 years; Mage at T2= 10.86 years, Mage at T3=12.12 years; comprising 393 behavioral assessments and 362 structural scans). Among older children, volumetric growth in: (a) head and body predicted improvements in item-time memory, (b) head predicted improvements in item-item memory; and (c) right tail predicted improvements in item-space memory. The present research establishes that volumetric changes in hippocampal subregions differentially predict changes in different aspects of relational memory, underscoring a division of labor along the hippocampal anterior-posterior axis.

neuroscience↗