bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic analysis of exercise capacity and training responses in 129S1/SvImJ and NZW/LacJ mice (711.12)
Authors: Massett Michael , Avila Joshua , Kim Seung 
Published: June 2021

Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (‐0.65 ± 1.73 min) and 129S1 (4.31 ± 2.79 min) mice, a reciprocal intercross breeding scheme was used to generate 288 F2 mice. All F2 mice completed an exercise performance test before and after a 4‐week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = ‐10 to +12 min). Genome‐wide linkage scans were performed for pre‐training, post‐training, and change in run time. For pre‐training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (39.8 cM, 2.8 LOD). Suggestive QTL for post‐training exercise capacity were identified on Chrs 1 (52.0 cM, 2.2 LOD) and 5 (43.4 cM, 3.3 LOD). A suggestive QTL for the change in run time was identified on Chr 6 (37.8 cM, 2.9 LOD). To identify shared QTL, this data set was combined with data from a cross between B6 and FVB strains. In the combined cross analysis, a significant novel QTL for pre‐training exercise time was identified on Chr 12 (54.0 cM, 3.45 LOD) and a suggestive QTL for post‐training exercise capacity on Chr 8 (23.9 cM, 2.92 LOD). These data indicate that one or more QTL determine exercise capacity and training responses in mice.Grant Funding Source: Supported by NIH HL‐085918
microRNA‐21 expression analysis in mice (711.6)
Authors: Syed Maryam , Ball Jana , Miguel‐Hidalgo Jose , Romero Damian 
Published: June 2021

MicroRNAs (miRNAs) are endogenous, non‐coding RNAs that downregulate the expression levels of specific proteins by translational repression or mRNA degradation. miR‐21 has been implicated in cancer, development, immunity and cardiovascular diseases. However, miR‐21 expression at the cellular level in normal tissues remains controversial.The aim of the study was to analyze miR‐21 expression at the cellular level in normal mouse tissues using a novel transgenic reporter mouse that expresses β‐galactosidase (LacZ) under the endogenous miR‐21 promoter. Mir21tm1Mtm/Mmjax mice were crossed with CAG‐Cre mice to delete the neomycin/miR‐21 cassette and generate lacZ‐KO‐Mir21tm1Mtm/Mmjax mice. Tissues from 10‐week old male lacZ‐KO‐Mir21tm1Mtm/Mmjax mice were embedded in OCT, cryosectioned and LacZ detected by histochemistry.MiR‐21 was highly expressed in the cardiac fibroblasts and tunica media of coronary arteries, periportal hepatocytes, kidney collecting ducts, respiratory epithelium of the bronchus in the lung, and testis seminiferous tubules. In the CNS, miR‐21 was highly expressed in the brain white matter, corpus callosum, anterior commissure, striatum, posterior thalamus and medulla oblongata.Although miR‐21 is expressed in multiple tissues in the adult mice, its expression at the cellular level is highly restricted, suggesting still unexplored roles for miR‐21 in health and disease.Grant Funding Source: Supported by American Heart Association Grant 12SDG8980032.
Activation of mu‐opioid receptors in commissural nucleus tractus solitarius markedly depresses hypoxic, but not hypercapnic, ventilatory response in conscious rats (712.11)
Authors: Zhuang Jianguo , Lin Amy , Xu Fadi 
Published: June 2021

Activation of cNTS MORs blocks HVR and moderately depresses HCVR (↓30%) in anesthetized rats (Zhang et al, Anesthesiology 2011) in agreement with the cNTS synaptically receiving carotid body afferents and heavily expressing MORs. Because of synergistic effect of anesthesia on opioids’ impacts and projections of bronchopulmonary C‐fibers (PCFs) to the cNTS, we asked whether stimulation of cNTS MORs would alter HVR, HCVR, and PCF‐mediated apnea in conscious state. cNTS catheter guide was instrumented in the anesthetized rats with the right site ensured by lack of HVR following local injection of DAMGO (2.5 mM, 30 nl), a MOR agonist. After recovery from surgery, three groups of conscious animals were individually placed in a whole‐body plethysmograph to: inhale 10% O2 for 2 min or 7% CO2 for 5 min, or receive right atrial bolus injection of capsaicin (CAP, 1 μg/kg) before and 5 min after intra‐cNTS microinjection of DAMGO with and without previous local blockade of MORs by CTAP (10 mM, 30 nl). Microinjection of DAMGO into the cNTS decreased baseline VE (↓16%) mainly via lowering fR and reduced HVR and PCF‐mediated apnea (63% and 20%, P < 0.01) without effect on HCVR. Microinjection of DAMGO following CTAP failed to alter HVR. Our data suggest that cNTS MORs play a critical role in depressing respiratory chemoreflexes in conscious state and this influence is largely strengthened by anesthesia.Grant Funding Source: Supported by HL‐107462
Increased Ca2+ permeable ampa receptor expression following carotid body denervation in goats (713.2)
Authors: Miller Justin , Neumueller S , Muere C , Olesiak S , Daghistany A , Pan L , Hodges M , Forster H 
Published: June 2021

The mechanisms which contribute to the time‐dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. The initiation of neuronal plasticity often involves changes in Ca2+ permeability. Therefore, we tested the hypothesis that during recovery from the acute effects of CBD in goats, there is an increase in Ca2+ permeable GluA1R and GluN1R and/or a decrease in Ca2+ impermeable GluA2R expression at brainstem sites that contribute to respiratory control. We tested this hypothesis via optical densitometric (OD) quantification of medullary neurons immunostained with antibodies targeting GluA1R, GluA2R, and GluN1R at 5‐13 days or 30 days after bilateral CBD. CBD resulted in hypoventilation and a reduced CO2 chemoreflex, which both recovered significantly over 30 days post‐CBD. At 5‐13 days post‐CBD, GluA1 OD was unchanged from control goats, but GluA2 and GluN1 OD were reduced 15‐30% within 6 of medullary respiratory nuclei measured. However, at 30 days post‐CBD GluA1 OD remained unchanged, but GluA2 and GluN1 OD returned to control levels. We conclude that a shift toward Ca2+ permeable glutamate receptors 5‐13 days post‐CBD may initiate the recovery of ventilation after CBD. Furthermore, at 30 days post‐CBD the partial recovery of ventilation is maintained by relatively normal glutamate receptor expression.Grant Funding Source: Supported by National Heart, Lung, and Blood Institute Grants HL25739 and HL007852 and by VA
Prenatal nicotinic exposure increases pulmonary C neural response to capsaicin associated with upregulation of TRPV1 in nodose ganglia neurons (713.4)
Authors: Zhuang Jianguo , Zhao Lei , Zang Na , Xu Fadi 
Published: June 2021

We have reported that stimulation of pulmonary C‐fibers (PCFs) during hypoxia produces a long‐lasting apnea or lethal ventilatory arrest in rats and that PNE promotes apneic and lethal ventilatory arrest responses to hypoxia (5% O2 for 60 min) in rat pups. Here, we tested whether PNE‐induced apneic and lethal ventilatory arrest were of central origin without airway hyperreactivity (AHR). We further tested whether PNE enhanced pulmonary C neural response to capsaicin (CAP) associated with upregulation of TRPV1 in nodose ganglion neurons. In Ctrl and PNE‐treated pups, we recorded: i) diaphragm EMG during 5% O2 up to 60 min and ii) specific airway resistance (sRaw) response to increasing dose of aerosol methacholine (0, 3.125, 6.25, 12.5, 25 mg/ml) in conscious state; iii) pulmonary C neural response to right atrial bolus injection of CAP (1 μg/kg) in anesthetized and paralyzed state; and iv) TRPV1 mRNA expression in neurons of nodose ganglia (by RT‐PCR). PNE produced apnea and lethal ventilatory arrest concomitant with silence of diaphragm EMG and did not induce AHR. PNE increased pulmonary C neural firing response to CAP associated with upregulation of TRPV1 in nodose ganglia neurons. We conclude that PNE increases PCF sensitivity likely through increasing TRPV1 expression, contributing to the PNE‐promoted central origin of the apneic and lethal ventilatory arrest responses to hypoxia.Grant Funding Source: Supported by HL‐107462
RNA sequencing to profile transcriptional changes within the medullary raphe: potential mechanisms of central neuroplasticity driving the recovery of eupneic ventilation after bilateral carotid body denervation (713.7)
Authors: Mouradian Gary , Forster Hubert , Hodges Matthew 
Published: June 2021

Bilateral carotid body denervation (CBD) in rats elicits eupneic (resting) hypoventilation 1‐2 d post‐CBD, which relatively rapidly returns to baseline values (14‐15 d). We have previously shown increases in brainstem serotonin (5‐HT) turnover and the 5‐HT transporter (SERT) acutely after CBD, leading to the hypothesis that the recovery of eupneic ventilation following CBD may be associated and/or initiated by activation of the medullary raphe nuclei (MRN). To test this hypothesis, we collected medullary raphe tissue punches (~1mm3) from rats euthanized acutely (1‐2 days) after sham (n=11) or CBD (n=10), or 15 days after sham (n=10) or CBD (n=10) surgery. Eupneic PaCO2 was increased acutely (p<0.001) and chronically (p<0.001) after CBD compared to pre‐CBD control, but PaCO2 15 days post‐CBD was not different than time‐control sham rats demonstrating recovery following CBD. Total RNA was collected using a phenol‐chloroform extraction protocol and quantified/qualified using an Agilent Bioanalyzer. 100 – 600 ng of total RNA was collected with an integrity number of 7 or greater for all samples, indicating high RNA quality. 12 cDNA libraries were created (3 or 4 per group x 4 groups) using the Illumina TruSeq RNA Sample Prep LS protocol for mRNA sequencing, from which all 12 libraries yielded pure cDNA. Ongoing mRNA sequencing will allow for the eventual coupling of our comprehensive physiologic measurements with raphe gene expression to provide unique insights into potential mechanisms of recovery or plasticity ventilatory control after CBD.Grant Funding Source: Supported by NIHHL097033, T32HL007852.
Ventilatory and metabolic changes in a mouse model of chronic lung disease (713.9)
Authors: Do Jennifer , Powell Frank , Trisko Breanna , Rich Benjamin , Breen Ellen 
Published: June 2021

We measured changes in ventilatory and metabolic responses to acute hypoxia and hypercapnia in a mouse model of chronic lung disease. Baseline measurements were made before any treatment. Then we deleted vascular endothelial growth factor (VEGF) in the lungs using the Cre‐loxP strategy. Lungs of VEGF‐lung null mice were treated with adeno‐associated virus (AAV) expressing Cre‐recombinase; control mice were treated with AAV‐LacZ. Measurements were made 1 month later. Then we exposed mice to cigarette smoke (CS, 10 cigarettes/day, 5 days/wk via a nose‐only exposure system) and repeated measurements after 2 and 4 months. VEGF‐lung null and control mice gained weight for 1 month but both groups lost weight during the first 2 months of CS and gained weight by 4 months of CS. Ventilation decreased in normoxia or hypercapnia similarly in VEGF‐lung null and control mice after 4 months CS mainly because of decreased tidal volume. Ventilation normalized for CO2 production shows the same trend so arterial PCO2 should increase. More ventilatory and arterial blood gas measurements are planned after 6 months of CS to quantify the effects of this treatment on pulmonary gas exchange.Grant Funding Source: Supported by NIH RO1 HL‐081823, P01 HL‐091830
Vascular hyperreactivity in a rat model of bronchopulmonary dysplasia (715.2)
Authors: Shuster Taylor , Bates Melissa , Kleinertz Aaron , Mahan Sidney , Eldridge Marlowe 
Published: June 2021

Bronchopulmonary dysplasia (BPD) develops in ~30% of premature infants and is associated with decreased alveolar and vascular development. We hypothesized that BPD is also associated with vascular hyperreactivity to hypoxic and hyperoxic challenges. A rat model of BPD was created by exposing newborn Sprague Dawley rats to 95% O2 (BPD) for 8 days after birth. Controls (CTL) were exposed to 21% O2. At 21‐25 days old, rats were anesthetized and a Millar conductance catheter was inserted into the left ventricle to obtain cardiac output. A fluid‐filled catheter was inserted into the right ventricle (RV) to measure pressure. Rats were ventilated with 100% O2 (10 min), and 10% O2 (10 min) and pulmonary vascular resistance (PVR) was calculated for each condition by dividing the RV pressure by cardiac output. BPD rats had RV hypertension at baseline compared to CTL (31±5 mmHg vs 16±2 mmHg, p=0.028), largely caused by increased cardiac output. Contrary to our hypothesis, BPD rats demonstrated little change in PVR to hypoxia and hyperoxia, suggesting that vascular reactivity is impaired in BPD. Given the observed baseline RV hypertension in the BPD group, our future studies will aim to investigate the impact on myocardial contractility in this model.Grant Funding Source: Supported by NIH 5R01HL115061
Methylene blue protects against oleic acid‐induced acute lung injury in rats (718.2)
Authors: Silveira Ana Paula , Albuquerque Agnes , Vento Daniella , Nadai Tales , Neves Ariadne , Campos Débora , Celotto Andrea , Évora Paulo 
Published: June 2021

We aimed to evaluate the methylene blue (MB) effects in the lung tissue, with emphasis on capillary permeability, inhibiting the soluble guanylate cyclase (sGC) in oleic acid‐induced (OA) acute lung injury (ALI). Male Wistar rats under spontaneous breathing received 1) OA (100 or 200 mg/kg); 2) Pretreated group received MB 5 min before the OA infusion, and; 3) Treatment group received MB 2 hours after OA infusion. The MB was administered as an i.v. bolus followed by 2h of continuous infusion (3mg/kg/h). After 4 h, blood was collected for gasometry; bronchoalveolar lavage for total protein dosage and lung tissue for wet weight/dry weight (W/D) analysis, histology and amount of tissue nitric oxide (NO). ALI was characterized by the OA of 200mg/kg, the increased bronchoalveolar lavage protein and the relation W/D. The main results were: 1) It was not observed severe hypoxemia after 4 hours of ALI; 2) The pre‐treatment group showed a significant difference with lower protein quantification in bronchoalveolar lavage; 3) Although not statistically significant it was observed lower values of the W/D ratio and NO tissue in the MB groups; 4) Gross examination of the lungs revealed more severe injury in the untreated group, confirmed by histological examination whose main findings include increased infiltration of lymphocytes, alveolar membrane thickening and increased alveolar edema. These data suggest that the lung permeability decreases when MB is administered at an early stage OA‐induced ALI.Grant Funding Source: Supported by CNPq
Radiofrequency renal nerve denervation decreases blood pressure, sympathetic activity and renal norepinephrine content in spontaneously hypertensive rats (72.1)
Authors: Gao Juan , Kerut Edmund , Smart Frank , Kapusta Daniel 
Published: June 2021

Radiofrequency renal denervation (RF‐RDN) decreases blood pressure (BP) in patients with drug‐resistant hypertension. This study investigated the effects of RF‐RDN on sympathetic activity and BP (Systolic, SBP; Diastolic, DBP) in SHR. Methods Nineteen‐week old male SHR were instrumented with telemetry probes for chronic measurement of BP and BP variability (BPV). After 1‐week, control BP was measured in rats for 3 days. The next day SHR (n=6/group) were anesthetized and randomly received either bilateral Sham‐RDN or RF‐RDN of the renal arteries (Biosense Webster Stockert 70 generator and RF‐probe). BP was then measured in SHR for 8 weeks. Results Following RF‐RDN, SBP/DBP was significantly decreased the day after (153±8/102±4 mmHg) and throughout the post‐RDN study (4‐week SBP/DBP, 173±7/120±5; 8‐weeks, 171±6/116±4 mmHg) compared to pre‐RDN control levels (SBP/DBP, 187±9/130±5 mmHg). RF‐RDN significantly decreased the low frequency component of BPV in SHR with the peak attenuation observed at 8 weeks (LF/HF 2.2±0.2 vs 0.9±0.2); this correlated with a blunting of the hypotensive response to i.p. chlorisondamine in RF‐RDN rats. Finally, at the end of week 8, kidney norepinephrine (NE) levels in RF‐RDN rats (left, 10±10; right, 0.0±0.0 ng/g kidney) were dramatically decreased compared with levels from sham SHR (left, 130±10; right, 110±10 ng/g kidney). Conclusions These data demonstrate that in hypertensive SHR, bilateral RF‐RDN of the renal arteries decreases BP in part by chronic inhibition of sympathetic neural pathways and a decrease in renal tissue NE levels.Grant Funding Source: Biosense Webster grant IIS‐175 to DRK and FS; NIH NIGMS P20 GM103514 to DK
The Klingler preparation technique and plastination: orienting students to three‐dimensional neuroanatomy (721.9)
Authors: Jilwan Andrew , Shukla Vipul , Baptista Carlos 
Published: June 2021

Due to the complexity of the central nervous system, neuroanatomy is cited as one of the most challenging portions of the anatomical sciences to study by first year medical students, and junior physicians alike. Fiber paths are challenging to visualize to their full extent, and it is difficult for a novice learner to clearly dissect them. Interpretation of a two‐dimensional image to a three‐dimensional anatomical structure is a daunting task, and creates palpable dread to many students.Since its inception, plastination has served as an adjunct in teaching anatomy. If used properly, plastinated specimens can augment students' understanding of neural architecture. Brains dissected following the preparation method by Klingler can be plastinated and utilized for visualization of fiber paths, and used to accent complex structures. This technique can isolate neuroanatomical structures that students often have trouble visualizing in three dimensions, such as the corpus callosum. This poster will discuss the specimen preparation technique, as well as assessing the potential benefits for orienting students to three‐dimensional neuroanatomy.
Next generation anatomy: integrating whole genome sequencing within the human anatomy curriculum (723.2)
Authors: Kumar Akash , Smith Kelly , Clark John , Shendure Jay , Horwitz Marshall 
Published: June 2021

Advances in genomics have vastly outpaced clinical education in this area. To help address this problem, the UW has piloted the introduction of whole genome sequencing within our first year human anatomy course.Last year, thirteen first‐year medical students performed whole genome sequencing and analysis of a cadaver during the anatomy course. The patient expired with a diagnosis of idiopathic pulmonary fibrosis. Students participated in a dissection of the cadaver, and a pathologist highlighted the anatomical changes resulting from the disease. Students then worked collaboratively to complete a ~45× whole genome sequence and then analyzed this patient’s genome using various bioinformatics tools. The analysis identified a variant in mucin‐encoding MUC5B that was recently associated with pulmonary fibrosis.A year later, these students presented their findings to small groups (<20 students) of the new first year students and discussed the patient’s clinical history, the results of the dissection and genome sequencing.Our experience demonstrated the value of introducing whole genome sequencing within anatomy as an early entry point for establishing genotype‐phenotype associations in medical education.Grant Funding Source: Funding provided by University of Washington MSTP
Video game and mental rotation training improve spatial anatomy task scores (725.5)
Authors: Lapaine Pierre , Johnson Marjorie , Nguyen Ngan 
Published: June 2021

High scores in measures of mental rotation have been associated with improved spatial anatomy performance. Mental rotation training, such as video games as well as paper‐and‐pencil mental rotation tasks, has been shown to improve mental rotation scores. The purpose of the study is to determine whether video game or paper‐and‐pencil mental rotation training can improve spatial anatomy ability.Participants in the study (n=13), either medical or dental students, were asked to complete the Mental Rotations Test (MRT) and the Spatial Anatomy Task (SAT) to provide a baseline measure of their spatial ability and spatial anatomy knowledge, respectively. Based on MRT scores, participants were assigned to one of three groups: one that played 5 cumulative hours of the video game Tetris (n=3), another that completed the MRT daily over the span of a 5 days (n=4), and a control group that received no training (n=5). All participants were again asked to complete the MRT and SAT after training. Paired t‐tests were used to compare baseline and final test scores in each group.Preliminary results show that both the MRT group (p = 0.046) and the Tetris group (p = 0.014) significantly improved their total SAT scores, while the control group (p = 0.129) did not. Although more research is necessary to make definitive conclusions, the current study indicates that mental rotation training may be of benefit for students learning spatial anatomy.
Prenatal ethanol exposure reduces pyramidal cell size and postsynaptic density length in the CA1 region of the hippocampus in adolescent rats (726.2)
Authors: Lindsay Brianne , Patten Anna , Christie Brian , Nahirney Patrick 
Published: June 2021

Fetal alcohol spectrum disorder (FASD) is the leading cause of cognitive impairment in the Western world. The impact of the toxic effects of prenatal ethanol exposure (PNEE) on the development of memory regions of the brain remains unclear. To understand these effects, a rat model of PNEE was used to study structural elements of cornu ammonis 1 (CA1) of the hippocampus. Using light and electron microscopy, the density and size of pyramidal cell nuclei and synapses in the CA1 were quantified by morphometric methods in control and PNEE male rats at postnatal day 35 (P35). During gestation the blood alcohol content of pregnant dams ranged from 90‐150 mg/dl and average body weight of PNEE offspring rats was ~15% less than controls at P35. By light microscopy, the pyramidal nuclear area (as a measure of cell body size) was reduced by ~22% in PNEE rats when compared to controls (105.1 ±15.1 µm² vs 135.2 ±4.65 µm²). By electron microscopy, the spine shape and density of synapses within stratum radiatum was not significantly different between the two groups, however, the total combined length of post‐synaptic densities (PSDs) per test field (117µm²) was significantly less in PNEE rats (2157 ±121 nm vs 2523 ±192 nm, p<0.025, n=30 fields/group). These results indicate ethanol exposure in utero affects the size of pyramidal nuclei and overall receptive fields (PSDs) in adolescent PNEE rats and points to permanent effects or delays in maturation in the CA1 region of the hippocampus.Grant Funding Source: Supported by NSERC