bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Salt Diet Induces a Rapid Increase in Blood Pressure and Mortality in the Ren−/− Dahl SS Rats
Authors: Ilatovskaya Daria , Levchenko Vladislav , Zietara Adrian , Spires Denisha R. , Staruschenko Alexander 
Published: June 2021

Renin‐angiotensin system (RAS) is an important regulator of fluid balance and blood pressure (BP), demonstrated by the widely employed use of angiotensin receptor and/or ACE inhibitors to control hypertension in humans. Here we used the renin knockout (Ren−/−) rats generated on the Dahl Salt‐Sensitive (SS) rat background to address the question of BP development in the absence of renin.Ren−/− rats exhibit polyuria, lower body weight and mean arterial pressure (MAP) (65.9 ± 2.1 in Ren−/− rats vs 121.9 ± 1.9 mmHg in the wild type (WT) littermates). Baseline glomerular filtration rate (GFR) is also lower in the Ren−/− rats compared to WT littermates (0.54 ± 0.04 vs 0.19 ± 0.03 mL/min/100 g of body weight). To test the role of renin in the BP regulation during the development of salt‐induced hypertension, Ren−/− rats and their WT littermates were kept on 0.4% NaCl diet since weaning (normal salt, NS), and then challenged with sodium deficient (SD, 0.01% NaCl) or high salt (HS, 4% NaCl) diets. BP was recorded via telemetry, kidney function was evaluated by GFR measurements, and diuresis was assessed in metabolic cages.After 10 days of a HS dietary challenge, 24 hr urinary output, sodium excretion, GFR and BP were elevated in the WT littermates, as expected. After a HS diet was introduced to Ren−/− rats there was a very rapid raise in MAP in the Ren−/− rats (ΔMAP was 60.4 ± 7.1 mmHg over a 5‐day period, compared to 5.0 ± 0.4 mmHg in the WT littermates). In the Ren−/− group, HS diet caused mortality. Neither of Ren−/− rats survived more than 13 days (8 days if animals were instrumented with a telemetry device), which was not observed in the WT littermates. Additionally, Ren−/− rats fed a HS diet had an increase in diuresis and sodium excretion during the first 2–4 days, which was blunted before the terminal point. Following an initial increase, a dramatic decline in GFR was also observed in these rats. Furthermore, before the endpoint there was a spike in plasma sodium level (up to 180 mMol/L) in the Ren−/− animals challenged with a HS diet.SD diet did not significantly affect MAP or survival in either group within 12 days of the observations. All SD diet fed animals showed reduced urinary output compared to rats fed a NS diet; however, no difference was found in electrolyte excretion between groups fed a SD diet. GFR was not affected in either group fed a SD chow.Therefore, BP in the Ren−/− rat increases in response to a HS diet, which suggests an involvement of the non‐renin components in this mechanism. Furthermore, we demonstrated that Ren−/− animals are able maintain homeostasis when challenged a SD diet. These data open new avenues to understanding the role of RAS in SS hypertension.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Ischemic Preconditioning on Oxygen Uptake and Extraction Kinetics During Exercise in Normoxia and Hypoxia
Authors: Wiggins Chad C. , Constantini Keren , Paris Hunter , Mickleborough Timothy , Chapman Robert 
Published: June 2021

BackgroundExercise tolerance is strongly related the physiological components of the primary (PC) and slow components (SC) of oxygen uptake. Exercise tolerance is reduced in clinical populations and during acute exposure to altitude by factors affecting skeletal muscle oxygenation. The practice of ischemic preconditioning has been shown to improve exercise tolerance or performance in a variety of different testing methods, but the mechanisms behind the improvements in exercise tolerance following IPC are still unclear.MethodsThirteen men (age= 24 ± 4 years, V̇O2max= 63.1 ± 5.1 ml·kg−1·min−1) completed four randomized trials of each combination of hypoxia (FIO2 = 0.16) or normoxia (FIO2 = 0.21) with a resting pre‐exercise IPC protocol (4 × 5 min at 220 mmHg) or SHAM procedure. Following the IPC/SHAM protocol subjects completed two constant load cycling bouts at power outputs corresponding to 1) 15% below the normoxic gas exchange threshold (CL #1) and 2) 85% of normoxic V̇O2max (CL #2). Breath‐by‐breath V̇O2, oxyhemoglobin saturation, and skeletal muscle oxygenation/extraction (measured via near‐infrared spectroscopy) were continuously monitored throughout the trials. V̇O2 and NIRS kinetics were quantified using a single (for CL#1) or double (for CL#2) exponential term equation with independent time delays for the V̇O2/NIRS primary and slow components.ResultsThere was a significant effect of inspirate on deoxyhemoglobin time constant (τ) during CL#1 (Hypoxia: 5.58 ± 2.82 s vs. Normoxia: 8.01 ± 4.71s, P < 0.05) with no effect of IPC treatment (P = 0.84). During CL #2, there was a significant effect of inspirate on V̇O2 primary amplitude (PC) (Normoxia: 3.13 ± 0.36 L/min vs. Hypoxia: 2.92 ± 0.39 L/min, P < 0.05). IPC did preserve microvascular oxygen extraction during high‐intensity cycling (CL #2) in Hypoxia (IPC: 21.3 ± 11.0 μM vs. SHAM: 19.9 ± 9.9 μM, P < 0.05), but did not affect any of the NIRS or V̇O2 parameters in Normoxia.ConclusionOxygen uptake and peripheral oxygen delivery are compromised during high‐intensity exercise in hypoxia. Ischemic preconditioning prior to high‐intensity bouts is effective at mitigating the declines in microvascular oxygen extraction seen during exercise in hypoxia, however the rates (τ) of microvascular extraction and oxygen uptake are not altered following treatment with IPC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Incorporating Technology in Anatomy Education to Align with Educational Outcomes
Authors: McBride Jennifer 
Published: June 2021

Over the past few decades, computer‐based educational technologies such as multi‐touch screen interfaces, software‐based applications and now consumer grade augmented, virtual and mixed reality devices have been introduced in the anatomical sciences. Unfortunately, methodologies to evaluate the impact of these computer‐based learning interventions on undergraduate medical students' acquisition of knowledge remains deficient. In addition, the level of mental effort or cognitive load placed on the learner with these learning interventions is a source of rich debate. During this presentation, a brief review of current data regarding the use of these computer‐based educational tools, as well as essential elements to consider prior to the incorporation of technology in the educational environment will be discussed.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inspiratory Resistive (R) Load Endurance Testing in Normal Healthy Adults: Load compensation, effort sensation and affective perception.
Authors: Davenport Paul Wesley , Davenport Matthew Paul , Feinstein Justin , Khalsa Sahib , von Leupoldt Andreas 
Published: June 2021

Increased respiratory load is a key feature in various respiratory diseases, accompanied by ventilatory compensation, cognitive awareness and affective perception. Loaded breathing can occur from minutes to days requiring the individual to modulate their breathing pattern to maintain alveolar ventilation, minimize work of breathing and minimize aversive load sensations. Increased inspiratory load is associated with cognitive sensation of the load magnitude and affective escape behavior to reduce the aversive perception of loaded breathing. During exacerbations of lung diseases, an individual often must compensate for increased loads that exceed their ability to sustain alveolar ventilation. Yet it is difficult to assess the capacity of an individual to adapt to an increased respiratory load. The aim of this study was to determine the ventilatory and perceptual endurance response to a high magnitude inspiratory R load applied for 10 minutes. It was hypothesized that some individuals would be able to complete the task and other individuals would terminate the task early. It was further hypothesized that early termination of the task would be due to increased aversive affective awareness. Healthy participants were tested while breathing through a non‐rebreathing circuit with an inspiratory load R=50 cmH20/L/s. The individual respired with no‐load for 1 minute, then the load was applied for 10 minutes, followed by 1 minute of no‐load breathing. The subject was instructed that they could terminate the task at any time by removing the mouthpiece. Subjects estimated their perceived load intensity (MEInt) and unpleasantness (MEUn) every minute. Fear (MEF) was estimated before and after the load trial. Two of six subjects terminated the trial early. The ventilatory load pattern for all subjects was a load dependent increased maximum inspiratory pressure, decreased airflow, increased inspiratory duration and unchanged expiratory duration, increased total breath time, increased inspiratory volume, unchanged minute ventilation, PCO2 and PO2. The MEInt increased with the onset of the load, was constant throughout the task and was the same for individuals that completed and stopped the task. MEUn increased with the load onset with greater MEUn for subjects that stopped early. The individuals that stopped early had equal MEF at task onset but much greater MEF when the task stopped. The results suggest that inspiratory R50 endurance capacity is decreased in individuals with greater negative affective responses to high magnitude loaded breathing.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
ATP in the Lateral Hypothalamus/Perifornical area (LH/PFA) Increases CO2 Chemoreflex.
Authors: Dias Mirela Barros , da Silva Eliandra Nunes , Gargaglioni Luciane Helena , de Anchieta de Castro Horta‐Junior Jose 
Published: June 2021

The Lateral Hypothalamus/Perifornical area (LH/PFA) is a chemosensitive site and participates in the CO2 ventilatoy response in a vigilance‐state‐dependent manner. Studies provide evidence of a physiological role for ATP in central chemoreception. We tested the hypothesis that ATP acting on LH/PFA contributes to the CO2 ventilatory response. To this end, ventilation (VE) was recorded in unanesthetized rats by whole body plethysmograph, together with EEG and EMG. We dialyzed into the LH/PFA vehicle and then α,β‐methyleneATP (selective P2X receptor agonist; 10 mM) or PPADS (purinergic antagonist; 1 mM), and studied its effects on VE in air and hypercapnia (7% CO2) during the light and dark period of the diurnal cycle. During wakefulness, but not during sleep, α,β‐methyleneATP microdialysis augmented the hypercapnic ventilatory response by 25% during the dark‐active period (2288 ± 80 mL/kg/min) compared with its vehicle (1786 ± 161 mL/kg/min) (P< 0.01), but not during the light. This effect was due to an increased tidal volume. No effect was observed in normocapnia or in a separate group of animals who had the microdialysis probe misplaced (peri‐LH/PFA). PPADS did not change the ventilatory parameters in all groups. These results suggest that ATP exerts, in the LH/PFA, an excitatory modulation in the hypercapnic chemoreflex during wakefulness in the dark‐active period of the diurnal cycle.Support or Funding InformationFAPESPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gene Ontology Analysis of and Subtyping of Breast Tumors by RNA‐Seq and BiNGO
Authors: Soneral Paula , Skorseth Claire 
Published: June 2021

Breast cancer, the second deadliest among women, kills about 40,000 individuals worldwide per year. Such lethality is due, in part, to the inherent heterogeneity of breast cancer disease, posing challenges for clinicians to accurately diagnose and subtype tumors. Recently, RNA‐seq technology has made it possible to subtype and classify tumors using gene expression profiling. In this experiment, we validated the efficacy of using RNA‐seq gene expression technology as a diagnostic tool for breast tumor subtyping in the context of an undergraduate course. Publicly available datasets from the Sequence Read Archive (SRA) of MCF‐7 breast cancer cells were subjected to quality control analysis using the Green Line of DNA Subway (Tuxedo Pipeline, FAST‐X, FAST‐QC, Tophat, and CuffDiff algorithms). Log‐transformed gene expression ratios were subjected to the BiNGO gene ontology algorithm. Significant over‐expression of genes for metabolic and cellular processes pathways included cell death and cell division (p<0.01 Binomial). Significantly down‐regulated pathways included those in development (organ development, etc), regulation (stimulus response, inflammatory response, etc), and signaling (cellular communication, etc; p<0.01 Binomial). Furthermore, using previously established biomarker genes, we subtyped the cells as basal‐like ‐ showing little change in expression for Estrogen Receptor (ER), Her2/neu (HER), or Ki‐67 biomarkers, but a significant over‐expression of the progesterone receptor (q = .0031). Using the Mammaprint suite of biomarkers we diagnosed a highly progressed tumor, wherein 60% and 73% of the Mammaprint mid‐hallmark genes and 38% late hallmarks were differentially expressed. This analysis was corroborated by previous datasets from DNA microarrays. Taken together, our findings suggest that RNA‐seq sequence data can be a valid approach for subtyping human breast cancers, and determining progression of disease.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Investigation of the Effects of SULT2A1 Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone by Human Cytosolic Sulfotransferase SULT2A1
Authors: Abunnaja Maryam , Liu Ming‐Cheh 
Published: June 2021

The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of dehydroepiandrosterone (DHEA) as well as many other sterols and steroids. The present study was designed to investigate how genetic polymorphisms of the human SULT2A1 gene may affect the sulfation of DHEA. Online databases were comprehensively searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non‐synonymous coding SNPs identified, seven were selected for further investigation. Site‐directed mutagenesis was used to generate cDNAs encoding these seven SULT2A1 allozymes, which were expressed in BL21 E. coli cells and purified by glutathione‐Sepharose affinity chromatography. Enzymatic assays revealed that purified SULT2A1 allozymes displayed differential sulfating activity toward DHEA. Kinetic analyses showed further differential catalytic efficiency and substrate affinity of the SULT2A1 allozymes, in comparison with wild‐type SULT2A1. These findings provided useful information concerning the effects of genetic polymorphisms on the sulfating activity of SULT2A1 allozymes.Support or Funding InformationThis work was supported in part by a grant from National Institutes of Health (Grant # R03HD071146).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Binding of 4‐hydroxy‐2‐nonenal Decrease Non‐enzymatic Methemoglobin Reducing Capacity
Authors: Wilson Parker , Mowery Colin , Ramanathan Ranith 
Published: June 2021

Lipid peroxidation can produce reactive primary and secondary oxidation products. Various studies have shown that secondary lipid oxidation products, such as 4‐hydroxy‐2‐nonenal (HNE), can bind with proteins and minimize their functional properties. Hemoglobin is the primary oxygen‐carrying protein and can exist in three different forms; oxyhemoglobin, deoxyhemoglobin, and methemoglobin. Oxyhemoglobin/deoxyhemoglobin can carry oxygen, while the oxidized form, methemoglobin, cannot. Physiologically, methemoglobin can be converted to deoxyhemoglobin by enzymatic and non‐enzymatic reduction. Studies have shown that HNE can preferentially bind with histidine and lysine residues within a protein by Michael addition; Hemoglobin has several histidine and lysine residues in alpha and beta structures. However, limited studies have determined the effects of HEN binding on non‐enzymatic methemoglobin reducing capacity. The overall goal of this study was to determine the effects of HNE on non‐enzymatic methemoglobin reducing capacity. Equine hemoglobin (0.1 mM) was pre‐incubated with HNE (0, 0.1, and 0.7 mM) at pH 7.4 and 37 °C for 5 hours to promote covalent binding of HNE to methemoglobin. Following pre‐incubation, methemoglobin was combined with methylene blue and EDTA. The non‐enzymatic reduction was initiated by the addition of NADH and the reduction of methemoglobin was monitored using a UV‐Vis spectrophotometer. Methemoglobin reduction was expressed as nanomoles of methemoglobin reduced per min. The experiment was replicated three times. Pre‐incubation of HNE decreased (p < 0.05) non‐enzymatic methemoglobin reducing capacity. There were concentration‐dependent effects of HNE on non‐enzymatic reduction. Methemoglobin reduction was decreased (p < 0.05) by 17% for 0.1 mM HNE compared with control methemoglobin, however, there was 60% decrease (p < 0.05) in non‐enzymatic methemoglobin reducing activity with 0.7 mM HNE. Lipid peroxidation in various physiological and pathological conditions can increase HNE level in tissue and plasma. The current study suggests that HNE can decrease non‐enzymatic hemoglobin reduction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Subcellular Distribution of the Dopamine Transporter Phosphorylated on Threonine 53
Authors: Gilchrist Thomas J. , Gaarder Zachary S. , Hovde Moriah J. , Vaughan Roxanne A. , Foster James D. 
Published: June 2021

Dopamine (DA) is a catecholamine neurotransmitter, which controls many physiological and psychological processes including reward, motivation, attention, and motor activity. Disruption of DA homeostasis has been implicated in a number of neurological diseases such as attention‐deficit hyperactivity disorder (ADHD), schizophrenia, depression, addiction, and Parkinson's disease. The dopamine transporter (DAT) is a plasma membrane protein that functions to move extracellular dopamine back into presynaptic neurons and is the primary means by which DA is cleared from the extraneuronal space. DAT is also a site of action for psychostimulant drugs such as cocaine and amphetamines, as well as therapeutic drugs such as methylphenidate and bupropion that are used to treat ADHD and depression respectively. Studying DAT function and its regulatory elements is crucial to better understand the pathophysiology of dopaminergic disorders, and to identify and improve treatments for these disorders. DAT activity is controlled by post translational modifications including ubiquitination, palmitoylation and phosphorylation. Phosphorylation occurs on two domains within the DAT N‐terminus: a protein kinase C (PKC) domain at the distal end containing serine 7 within a serine cluster and a proline‐directed mitogen activated protein kinase (MAPK) site at threonine 53 proximal to transmembrane domain 1. We have recently developed an antibody that specifically recognizes pT53 DAT and have utilized this tool to further investigate the functional importance of DAT T53 phosphorylation using fluorescent immunocytochemistry and confocal microscopy to determine subcellular localization of pT53 DAT in comparison with a pan antibody for total DAT (MAB16). Our preliminary results using two cell models (LLC‐PK1 and N27 neurons) expressing rat DAT suggest that pT53 DAT is found at the plasma membrane and extensively throughout the cytoplasm displaying a distinct and intense punctate pattern while fluorescence detected with the pan MAB16 antibody was most intense at the plasma membrane with some intracellular punctate staining. These initial studies create a foundation for additional studies that will include fluorescent subcellular markers and treatments that modulate DAT phosphorylation at threonine 53 which may further our understanding of the functional relevance of DAT phosphorylation at this site and provide potential insight for involvement of dysregulation of DAT phosphorylation in dopaminergic disorders.Support or Funding InformationSupport: National Institutes of Health grants DA 031991 (JDF), DA13147 and 5P20‐104360 (RAV), P30‐GM103329 (UND), P20‐GM12345 (UND)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Mesenchymal Stem Cells on Qualitative and Quantitative Characteristics of Energy Transformation in Muscle Tissue of Lower Extremity in Ischemia.
Authors: Shypilova Inna , Gami Rakesh 
Published: June 2021

Energy transformation required for the performance of multiple energy dependent functions of the body, i.e. mechanical, chemical, and electrical, is important part of cell activity. Energy dependent functions become slower at intracellular level due to decreased ATP by 10–15% and stops completely with 25–30% decrease in ATP in the cell. Adenylic nucleotide concentration measures the mismatch between the energy demand and energy production in the cell's mitochondrial oxidative phosphorylation.A study was done with pubescent Wistar rats with body mass of 160–200 grams. The ischemia of the lower extremities was achieved by ligation of femoral artery. Bone marrow was taken from femoral, humoral and tibial bones. Cell culture was grown in Eagle medium IGLA MEM, enriched with L‐glutamine, 10% calf embryo serum with antibiotics added and 5 million of cell were injected intramuscularly in the experimental animals. The concentration of ATP, ADP and AMP in the gastrocnemius muscle measured by means of thin‐layer filtration on silica gel plates on 3rd, 5th, 7th, 14th, 21st and 28th day after injection of mesenchymal stem cells (MSC).The concentration of ATP decreased significantly in the control group after ischemia in consecutive study on specified days. It has been proved that MSC ejection redistributes the pool of adenylic nucleotides towards the increased ATP biosynthesis, so that such parameters of energy metabolism as energy charge, energy potential, thermodynamic control of respiration are increased and the correlation between the components of adenylate kinase reaction is decreased.This study showed that the ability of MSC provide protective action on energy homeostasis by means of the synthesis of large amount of cytokines and growth factors which stimulate the synthesis of glycolytic and Krebs cycle enzymes, increase glucose utilisation and ATP synthesis. Thus, activation of ATP synthesis restores the level of ATP and high energy phosphate bonds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.