bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Carbon Dots Cross the Blood-Brain Barrier and Preferentially Target Spinal Neurons
Authors: Parikh Komal , Seven Elif , Luca Edward , Mitchell Gordon , LeBlanc Roger , Seven Yasin 
Published: May 2023

The spinal cord processes and transmits neural signals controlling sensorimotor functions (e.g., breathing, locomotion, and bladder control). Disorders of the spinal cord, such as spinal cord injury and neurodegenerative diseases, often impair sensory and motor functions, causing morbidity and mortality. Therefore, it is important to develop drug delivery platforms to deliver the therapeutics directly to the spinal cord (availability) and target specific cell populations (specificity). Nanoparticles have been used as effective delivery platforms for drugs. However, whether those nanoparticles can target desired cell types in the spinal cord remains unknown. Here, we hypothesized that glucose-based carbon dots (GluCDs) cross the blood-brain barrier (BBB) and localize to neurons in the spinal cord. To test this hypothesis, we injected Sprague-Dawley rats with GluCD-fluorescein nanoconjugate intravenously. Fluorescein enabled visualization of spinal cord nanoparticle distribution and mimicked a small molecule drug cargo. Four hours post-injection, spinal cords were harvested, fixed in paraformaldehyde overnight, and cryopreserved. Tissues sections (40-μm thickness) were analyzed for cell-type colocalization with GluCD-fluorescein conjugate in the green channel and cell markers in the red channel. We used NeuN (neuronal marker), GFAP (astrocyte marker), and IBA1 (microglial marker) to label different cell types. We quantified colocalization in 3 ways: 1) Percent colocalization with different cell types, 2) 2-dimensional cross-correlation analysis with MATLAB, and 3) Positive/negative classification by 2 independent operators. Colocalization analyses demonstrated that GluCD-fluorescein nanoconjugates crossed the BBB and significantly colocalized with spinal neurons in ventral, intermediate gray, and dorsal regions. ~95% of the GluCD-fluorescein nanoparticles colocalized with neurons, and ~4% colocalized with microglia. There was no colocalization of GluCD-Fluorescein with GFAP-positive astrocytes. Thus, GluCD nanoparticles penetrate the BBB and colocalize with neurons, making them highly novel and promising neuron-specific drug delivery platforms for spinal cord injury and neurodegenerative diseases. Supported by: NIH R21NS119862-01 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Feasibility of using radiolabeled nitrogen-13 to track nitrogen kinetics in rodents exposed to hyperoxia or hyperbaric pressure.
Authors: Ashworth Edward , Ogawa Ryotaro , Vera David , Lindholm Peter 
Published: May 2023

Decompression sickness occurs from tissue supersaturation with nitrogen when pressure is reduced. It limits operational capacity in diving, aviation and extravehicular activity in space. Little is known about organ variability, and why differences exist between individuals. Procedures are based on empirical testing and mathematical modelling, with limited data from actual nitrogen load or diffusivity. Nitrogen has a positron-emitting isotope that can be made in gaseous form (13N2) which can then be monitored spatially and temporally. The feasibility to study nitrogen kinetics was assessed using hyperbaric pressure to increase the partial pressure or pre-breathing oxygen to increase tissue uptake capacity, both of which would expect to cause increased nitrogen uptake. Fifteen female Sprague Dawley rats were divided into air-breathing normobaric (CON), oxygen-breathing, including 1 h pre-breathing (OXY), and air-breathing hyperbaric, compressed to 700 kPa (HB). Breathing gases were supplemented with trace amounts of 13N2 for 30 min, with CON & OXY euthanized at 30 min. HB were decompressed and breathed air/isoflurane without 13N2 for 10-15 minutes before euthanized. Blood, liver, brain, femur (bone) and thigh muscle were analyzed in a gamma counter with the 13N2 counts normalized for organ mass. In liver (p=.026) and brain (p=.018) 13N2 was greater in OXY than both CON and HB. In the femur HB was higher than CON (p=.048). Results suggest that pre‑breathing O2 in OXY removed tissue nitrogen creating a larger gradient for 13N2 uptake. We interpret the limited increase in 13N2 in HB was due to off-gassing in high-perfused tissues during decompression, with the high femur value being due to uptake in HB but slower off-gassing during decompression. Our data suggest that 13N2 can be used to track gas kinetics in a live rodent during physiological conditions endured by humans. This study was supported by a grant from the Office of Naval Research. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Influence of aerobic exercise on cognitive function in the TgF344-AD model of Alzheimer's disease
Authors: White Zachary , Young Michael , Hall Stephanie 
Published: May 2023

Introduction – Exercise therapy is a promising strategy for Alzheimer’s disease (AD) protection although our understanding of exercise-induced neuroprotection remains incomplete. The goal of the present study is to longitudinally characterize the influence of exercise training on changes in cognitive function in both male and female TgF344-AD rats. We hypothesize that cognitive function will be impaired by AD and exercise-training will rescue AD-induced impairments. Methods – Male and female TgF344-AD rats (n=62) began a six-month progressive treadmill training protocol at 12 months of age. Training was conducted 5 days per week and intensity maximized at 24 meters per minute for 60 minutes. Behavioral testing, including Morris Water Maze (spatial learning and memory), Rotarod (motor coordination), and grip strength (muscular strength), was conducted at months (m) 3, 6, 9, 12 (pre-intervention), and 13-18 (post-intervention). Investigators were blind to presence of AD. Differences were identified with Bayesian multivariate linear regression. Results – Memory (latency time, s) was rescued by exercise in female AD rats. Post-intervention, female exercise groups demonstrated improved memory (-0.02 log scale s/m) while sedentary controls declined; no exercise effect was detected in male wild-type (WT) or AD groups. Grip strength is represented relative to body weight (g/g). Post-intervention, average grip strength declined across all groups and declines were greater in AD compared to WT animals (-0.038 vs -0.011 log-transformed g/g per month). Exercise attenuated the age-related declines compared to sedentary controls (0.001 vs -0.0498).The rate of grip strength loss from 13 m to 18 m was one-eighth the rate in female AD exercisers compared to female AD sedentary (-0.009 vs -0.075) while male AD exercisers lost strength at one-fourth the rate compared to male AD sedentary (-0.013 vs -0.054). Conclusions – In the present study the influence of advanced age, AD genotype, and exercise training in the TgF344-AD rat manifested in a sex-specific manner. In females, exercise training ameliorated AD-induced memory deficits and ameliorated age- and AD-induced strength declines to a greater degree than males. Our time-wise characterization of memory and grip strength in the TgF344-AD rat provides valuable reference for future biochemical analysis aimed at elucidating mechanisms of exercise-induced neuroprotection. R03 AG065970, P20GM113109 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Low-dose opioid analgesics (Morphine, Fentanyl, and Sufentanil) do not produce profound cardiovascular effects or reduce survival time in a rat model of traumatic hemorrhage
Authors: Marshall Stephanie , Marshall Stephanie , Ryan Kathy , Calderon Mariam , Connor Bryan , Hinojosa-Laborde Carmen , Klemcke Harold 
Published: May 2023

Objective: To determine the impact of analgesic doses of opioids on cardiovascular function and survival time in a severe hemorrhage and extremity trauma rat model. Hypothesis: Using opioids for appropriate pain management, not sedation, will not exacerbate the pathophysiological shock process in a model of polytrauma. Background: Morphine has been doctrinally discarded for use in pain management following battlefield hemorrhage due to its effects on cardiovascular suppression. However, the effects of new opioids, Fentanyl and Sufentanil, on cardiovascular function have yet to be fully described. The current study was conducted to evaluate and compare effects of three opioid analgesics on cardiovascular function and survival after severe hemorrhage in conscious rats in the presence of extremity trauma (ET). Methods: Male rats (n=10/group) were randomly assigned to receive either 0.9% saline (S), 2.0 mg/kg morphine (M), 10 μg/kg fentanyl (F) or 1 μg/kg sufentanil (SuF). Two weeks prior to experimentation, rats were surgically implanted with a telemetry unit to measure mean arterial pressure (MAP) and heart rate (HR). A carotid catheter was then placed. After 24 hours, rats were anesthetized briefly to undergo soft tissue injury and fibula fracture. Rats were allowed to awaken, and 90 min later underwent a conscious hemorrhage (~50% of blood volume). At the end of hemorrhage, rats received one dose of either S, M, F, or SuF via the carotid catheter. Rats were observed for a maximum of 4 hr after the start of hemorrhage. Results: From 70 to 195 min after the end of hemorrhage, there was a significant (p≤0.04) decrease in the MAP of M rats relative to that of V rats, while SuF decreased MAP (p≤0.02) only at t=100, 220 and 240 min. There was no significant effect of treatment on HR (p=0.37) throughout the experiment. Neither survival times (p=0.88) nor percent survival (p=1.0) differed between treatment groups. Conclusions: At the analgesic dose previously shown to ameliorate behavioral indices of pain in rats, both M and SuF depressed blood pressure following severe traumatic hemorrhage. Despite this hypotensive effect, none of the opioids tested decreased survival time or survival rate. Funding disclosure: Applied Pain Research Program, US Army Clinical and Rehabilitative Medicine/Joint Program Committee 8, and US Army Combat Casualty Care Research Program, US Army Medical Research and Development Command. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Tools for studying enteroendocrine cell subtype development and physiology in zebrafish
Authors: Morash Margaret , Kay Richard , Wen Jia , Padilla-Mercado Gilberto , Ye Lihua , Reimann Frank , Gribble Fiona , Rawls John 
Published: May 2023

Enteroendocrine cells (EECs) are sensory cells in the intestinal epithelium that respond to ingested nutrients and microbial products in the gut lumen by releasing over 30 different hormones and neurotransmitters. These signaling molecules travel throughout the body to influence a wide variety of metabolic functions, including glucose metabolism, satiety, and gut motility. EECs are typically divided into subtypes based on their predominant hormone. As enteroendocrine hormones have different and sometimes antagonistic metabolic effects, this subdivision enables fine-tuned control of metabolism in response to a variety of stimuli. While many aspects of EEC development and physiology have been defined, the mechanisms underlying EEC subtype-specific development and physiologic adaptations to diet and microbiota remain largely unknown. To investigate these questions, we recently established zebrafish as a model system for studying EEC physiology. The optical transparency of larval zebrafish enables live imaging to observe EEC adaptations in vivo and in real time. We used single-cell RNA sequencing to profile sorted intestinal epithelial cells from zebrafish larvae and identified secretory lineages including 7 EEC subtypes that we identified by expression of EEC hormones and transcription factors. Many zebrafish EEC subtypes we identified correlate with subtypes described in the mammalian small intestine, suggesting an evolutionary preserved role for EEC subtypes in regulating animal physiology. We also conducted LC-MS/MS peptidomics on EECs sorted from adult zebrafish intestine to reveal extensive homology in EEC hormone peptide sequence and post-translational processing. Using this information, we have begun to create transgenic lines to label and manipulate each of the EEC subtypes. For example, we identify a single EEC subtype that expresses genes encoding ghrelin, somatostatin, and glucose dependent insulinotropic peptides. Peptidomic analysis reveals striking conservation in their posttranslational processing including octanoylated and decanoylated isoforms of the ghrelin peptide. We have generated a transgenic line using the ghrelin gene and are using it to test how the number, distribution, and function of ghrelin positive cells vary as a function of diet and microbial colonization status. Establishment of a toolkit for zebrafish EEC subtype biology will provide an important alternative to the prevailing mammalian models and help unravel their unique developmental programs, physiologic functions, and adaptations to environmental variables. NIH R01-DK093399 and the Gordon & Betty Moore Foundation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Chronic sodium-glucose co-transporter 2 (SGLT2) inhibition reduces renal sympathetic nerve activation and fluid retention in rats with congestive heart failure
Authors: Zheng Hong , Liu Xuefei , Patel Tapan , Patel Kaushik 
Published: May 2023

Congestive heart failure (CHF) is a pathophysiological state characterized by the activation of neurohumoral systems and sodium and water retention. Previously we have shown enhanced tonic renal sympathetic nerve activation in CHF increases the expression and functional activity of renal sodium-glucose co-transporter 2 (SGLT2). This study was to investigate the beneficial effects of chronic SGLT2 inhibition on renal sympathetic activity in CHF. Three weeks after coronary ligation surgery to induce CHF, Sprague Dawley rats were treated with SGLT2 inhibitor dapagliflozin (1mg/kg/day) via subcutaneous infusion for two weeks. Cardiac function, hemodynamic parameters, renal sympathetic nerve activity (both efferent and afferent activity), and renal excretory function were monitored. Compared with saline infusion, dapagliflozin significantly attenuated left ventricular end-diastolic pressure (13.6 ± 3.7 vs. 20.3 ± 3.9 mmHg, P<0.05) in rats with CHF. A slight decrease in mean arterial pressure was observed by telemetry in dapagliflozin-treated CHF rats. Dapagliflozin infusion increased urine volume (18.6 ± 3.1 vs. 9.2 ± 3.8 ml/day, P<0.05) and sodium excretion (4.8 ± 1.0 vs. 2.0 ± 0.6 mEq/day, P<0.05) in CHF rats. In CHF rats, dapagliflozin reduced urinary norepinephrine excretion (4.6 ± 0.4 vs. 8.3 ± 0.7 ug/day, P<0.05), basal renal sympathetic nerve activity (2.1 ± 0.3 vs. 3.8 ± 0.4 uV.s, P<0.05), and renal afferent sympathetic nerve activity (35.6 ± 5.7 vs. 58.4 ± 5.8 %Amax, P<0.05). These data suggest that chronic long-term treatment with SGLT2 inhibition exerts a potential protective effect on CHF through attenuating renal afferent and efferent sympathetic activity and consequent reduction in sodium retention. Funded by NIH R01-DK-114663 & R01-DK-129311 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Beta-Adrenergic stimulation is necessary but not sufficient to promote CIH-induced Multiple Myeloma progression
Authors: Johnson Olivia , Vasileva Anastasiia , Vasilyev Mikhail , Lane Carter , Kalra Hardik , Jedlicka Charlie , Berschel Mackenzie , Tomasson Michael , Bates Melissa 
Published: May 2023

Multiple myeloma (MM), a terminal cancer of bone marrow plasma cells, affects about 35,000 people yearly, and kills 13,000. The KaLwRij mouse model spontaneously develops pre-malignant myeloma disease (MGUS) and is receptive to myeloma development. In the C57BL/6 mouse model, chronic intermittent hypoxia allows lethal engraftment of malignant myeloma cells. Our central hypothesis is that myeloma susceptibility in both models is modulated by the sympathetic nervous system and beta-adrenergic receptor activation. 8 - week old C57BL/6 female mice were exposed to either propranolol, isoproterenol, or saline for 6 weeks. At week 2, mice were injected with either 5TGM1/GFP+ (MM) cells or saline. Heart rate and heart rate variability were collected using MouseOx and LabChart Pro to monitor expected drug effects. All animals were monitored for terminal paralysis. Bone marrow and spleen cells were harvested for qPCR analysis to quantify 5TGM1 cell proliferation. C57BL/6 mice did not have decreased survival when treated with isoproterenol, but propranolol was protective against CIH-induced MM susceptibility. Propranolol did not increase survival in KalwRij mice. In order for Multiple Myeloma to progress in the CIH mouse model, β2-adrenergic receptor activation is required but is not sufficient. This experiment can be used to understand the role of sympathetic nervous system stimulation and its contribution to MM engraftment and growth. Supported by NIH 1R56HL152365. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Automated analysis of smooth muscle calcium sparks in line-scan recordings of intact arteries
Authors: Nelapudi Nikitha , Boskind Madison , Williamson Grace , Juarez Rucha , Zhang Lubo , Blood Arlin , Wilson Christopher , Puglisi Jose , Wilson Sean 
Published: May 2023

Activation of ryanodine receptors on the sarcoplasmic reticulum are well known to cause subcellular rapid Ca2+ events that are commonly referred to as Ca2+ sparks. These Ca2+ spark events regulate vascular reactivity through activation of potassium channels on the plasma membrane. Intracellular Ca2+ signals are commonly examined using fluorescent imaging approaches using high speed confocal microscopes. Over the past two decades, analysis of these events has advanced from visual observation and manual analysis by trained observers to more automated approaches. The purpose of the current study was to test whether fully automated approaches could accurately detect Ca2+ sparks in line-scan images and analyze spatial and temporal aspects to the events. This evaluation was addressed by re-analyzing a published “gold standard” dataset, where original analysis was performed through experimenter guided analysis of Ca2+ signals from recordings made in pulmonary arterial myocytes of en face arterial preparations. Ca2+ sparks were detected and analyzed automatically post-hoc using a customized Ca2+ spark analysis program, Sparklab 5.8. Increasing the threshold for detection led to incremental decreases in the percentage of cells with activity and the firing frequency. Raising the threshold also impacted the PPV, sensitivity and false discovery rate, which was examined through comparison to visually observed Ca2+ spark events. Interestingly, changing the threshold had little impact on spatial and temporal aspects of the Ca2+ spark events. Overall, automated Ca2+ spark detection and analysis with Sparklab 5.8 is expected to greatly improve experimental workflow and can be well optimized with low false discovery rates and reasonable levels of sensitivity. NIH R01HL155295, R01HL149608 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Physiological Significance of Macula Densa Neuronal Nitric Oxide Synthase-1 in Renin Release and Renin-dependent Blood Pressure Maintenance
Authors: Liu Catherine , Parris Colby , Naeem Muhammad , Wang Lei 
Published: May 2023

The role of macula densa nitric oxide synthase 1 (NOS1) in regulation of renin release is controversial. This study was conducted to further elucidate the role of macula densa NOS1 in renin release and blood pressure regulation in response to salt challenges and hemorrhagic shock.Tissue specific macula densa-NOS1 knockout (KO) and wild type (WT) mice were given low (0.1% NaCl) and high (1.4% NaCl) sodium diets or induced hemorrhagic shock by retro-orbital bleeding of 0.4 ml blood. Mean arterial pressure (MAP) was measured by radio-telemetry system. Plasma renin concentration (PRC) was determined by radioimmunoassay.PRCs were 496 ± 74 and 552 ± 68 ng/ml/hr in WT and KO mice fed a normal sodium diet, respectively. Low salt intake stimulated the renin release by about 220% in WT mice (PRC = 1364 ± 217 ng/ml/hr) compared to the level of normal salt diet, however, the stimulation was significantly blunted in KO mice (PRC = 688 ± 104 ng/ml/hr). High salt intake suppressed the PRC to the level of about 61% of PRC under normal salt diet. Deletion of macula densa-NOS1 further inhibited renin release to 43% of the levels of normal salt diet.Hemorrhagic shock induced about a 3-fold increase in PRC in WT mice, while only about 54% increase in the KO mice. The MAP values were significantly higher in WT mice than in KO mice during the first 6 hours following hemorrhagic shock. Thus, WT mice showed much quicker recovery in MAP than KO mice.Our study demonstrated that macula densa NOS1 plays an important role in mediating renin release. This mechanism is essential in maintaining blood pressure under hypovolemic situations such as hemorrhagic shock. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.