bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypercapnia Upregulates Expression of the NH3/NH4+ Transporter Rhbg in the Kidney
Authors: Nakhoul Nazih L , Hering‐Smith Kathleen , Hamm L. Lee , Islam M. Toriqul , Abdulnour‐Nakhoul Solange 
Published: November 2023

Hypercapnia occurs in patients with acute and chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome and is a major cause of increased mortality in hospitalized sick patients with COPD or cystic fibrosis. The kidneys compensate for respiratory acidosis by increasing urinary acid excretion (predominantly as NH3/NH4+) and de‐novo production of HCO3−. The mechanisms responsible for increased renal NH3/NH4+ excretion are not well known. In this study, we investigated whether the renal NH3/NH4+ transporters, Rhbg and Rhcg, are affected by hypercapnia. Using H+‐selective microelectrodes, we showed that CO2 caused a faster intracellular pH (pHi) decrease in oocytes expressing Rhbg as compared to H2O‐injected oocytes (−47 vs −17 × 10−4 pH/sec) indicating enhanced CO2 transport by Rhbg. Using In‐Cell Western, we showed that inner medullary collecting duct IMCD3 cells (that express Rhbg and Rhcg) grown on semi‐permeable membranes had a dramatic increase in Rhbg expression after 48 hours exposure to 20% CO2. Rhcg expression followed a similar pattern but the proportional increase in expression was smaller. In a series of in‐vivo experiments in mice, we induced respiratory acidosis by placing the mice in special chambers where the breathing gas mixtures were 8% CO2 (balance 21% O2 & 71% N2). Control group breathed normal air. After 4 days, the kidneys were extracted and Rhbg protein expression was assessed by Western analysis. Our data indicate that in hypercapnia Rhbg expression was increased by 23%, compared to control (n=5, p<0.05). These results indicate that CO2 is transported by Rhbg and that respiratory acidosis upregulated Rhbg expression. Enhanced cellular CO2 transport, due to elevated CO2 in respiratory acidosis and/or changes in acid‐base status, may be responsible for upregulating expression of the renal NH3/NH4+ transporter Rhbg.Support or Funding InformationVA Merit grant, NIH‐RO1 and Tulane Institutional Fund
The Local Vascular Activity of Norepinephrine (NE) in Renal Perivascular Adipose Tissue (PVAT)
Authors: Restini Carolina Baraldi A. , Burnett Robert , Fink Gregory D. , Watts Stephanie W. 
Published: November 2023

Perivascular adipose tissue (PVAT) is implicated in the pathophysiology of cardiovascular disease, especially in obese individuals in which the quantity of PVAT is markedly increased. We have shown previously that PVAT around the aorta and mesenteric arteries contains releasable norepinephrine (NE) that can constrict the underlying arteries. Although obesity in known to be especially associated with increased noradrenergic activity to the kidneys, and PVAT is found adjacent to the main renal arteries and their primary branches, it is not known if NE derived from PVAT affects the tone of the renal vessels. Therefore, in this study we tested the hypothesis that PVAT around the main kidney artery contains sufficient releasable NE to cause arterial contraction. Tissue NE concentration was measured by High Performance Liquid Chromatography (HPLC). Isometric vascular contractility studies were performed using endothelium intact rings (2 mm) from the main renal artery of normal male Sprague‐Dawley rats. Some rings were studied with PVAT still attached (+PVAT), while others had PVAT removed (−PVAT). Tyramine (Tyr), an indirectly acting sympathomimetic, was used to test for the presence of a functional NE pool in PVAT. Tyr concentration‐response curves (10−8–10−3M) were constructed in the presence of nisoxetine [a NE transporter inhibitor (Nxt: 1 μM)] or vehicle (water). Prazosin (Pz: 1μM), an α1‐adrenoreceptor antagonist, was added after the maximum contraction‐induced by Tyr was obtained. NE concentration (ng/g tissue) was high in main renal arteries and their branches of −PVAT strips (913.9±68.2; n=4) and in isolated PVAT taken from these vessels (523.7±68; n=5). Presence of PVAT did not alter the efficacy of Tyr‐induced contraction, indicated by the concentration to produce the maximum effect (+PVAT: 12.3±3.3mN, − PVAT: 14.5±1.3mN; n= 4–5) or the potency, indicated by the negative logarithm (−log) of half maximal effective concentration (EC50) (+PVAT: −4.1±0.1, − PVAT: −4.6±0.1; n=4–5). Similarly, both pharmacological parameters of Tyr‐induced contraction were not altered by the Nxt: after incubation with Nxt, the efficacy of Tyr‐induced contraction +PVAT was 14.4±3.1mN (n=8) and −PVAT= 10.9±2.9mN (n=5) and its potency +PVAT was −3.7±0.1 (n=8), and −PVAT= −3.74±0.2 (n=5). Pz reduced the maximum effect of Tyr by 90±5% in all of the rings. We conclude that Tyr‐induced contraction of the renal arteries is due to α1‐adrenoreceptor activation by release of NE in a manner independent of PVAT and the NE transporter. Furthermore, and contrary to our hypothesis, it is likely that the effects of Tyr are due exclusively to the release of NE from sympathetic nerves ‐‐ densely present in renal vessels – and not to release of NE from adjacent PVAT.Support or Funding InformationFAPESP (2015/25822‐9); HL70687.
Developmental Changes in Respiratory Inductance Plethysmography (RIP) Parameters
Authors: Shaffer Thomas H. , Balasubramanian Sona , Wang Yanping , Rahman Tariq 
Published: November 2023

RationaleMonitoring of respiration is crucial for rapid diagnosis, treatment, and critical care of patients in various clinical settings. The current noninvasive method for respiratory monitoring is (RIP) which requires post hoc analysis to calculate respiratory indices: respiratory rate (RR), phase angle (Φ), labored breathing index (LBI), and percent of ribcage contribution to breathing (%RC). Although studies have provided patient RIP values and corresponding age‐matched normal values; these studies lack global normative data for a wide age group.ObjectiveTo compile and calculate normative respiratory indices from studies including a large range of ages in order to develop a database of age‐dependent physiological values for (RIP) parameters.MethodsThe PubMed database, journals, reviews and book chapters were screened for RIP parameters in healthy individuals. Corresponding SEM or SD values are presented, along with number of subjects, age range (preterm infants to adults), sex, and body position. Based on regression analysis of RIP data vs. age; regression equations were calculated. Furthermore, 95% CI and 85% CI confidence intervals were derived.ResultsDepending on the RIP parameter, data from 200 – 900 subjects were utilized in the development of tables, graphs, and regression correlations. Since the database is rather large, we present only typical results herein, although data for all RIP parameters were analyzed. The correlation (R2=0.94; P< 0.001) between RR and postconception age was excellent (range: preterm infants to adults). As shown, the mean RR values were within or close to the 95% confidence intervals(Fig 1). The regression correlation between %RC and postconception age in years (number of data points, n = 36) was (R2 = 0.41; P<0.05).(Fig. 2).ConclusionThe presented database will provide caregivers with the ability to compare RIP data for patients with age‐matched normal controls, identify patients with higher risk of pulmonary complications and guide respiratory therapy. This is the first study that provides a compilation of normative RIP data across all age groups. This study has both research and clinical significance to further assist in early and rapid diagnosis of PF. Also, these data address the greater need to determine normative ranges for each WOB parameter for neonates and children. The regression graphs from the data analysis demonstrate that the greatest changes in RR with age occur during early development.Support or Funding InformationThis study was funded by The Nemours Foundation; The University of Delaware, Center for Advanced Technology (CAT) Program Grant #44058 (Tariq Rahman and Thomas H. Shaffer; CO‐PIs); and NIH COBRE Grant P30 GM114736 (Thomas H. Shaffer; PI).
Mas Antagonist Prevents the Anti‐inflammatory Effect of Exercise in a Model of Chronic Allergic Lung Inflammation
Authors: Campagnole‐Santos Maria Jose , Gregorio Juliana Fabiana , Magalhaes Giselle Santos , Motta‐Santos Daisy , Casssini‐Vieira Puebla , Barcelos Luciola , Rodrigues‐Machado M Gloria , Vieira Maria A R , Santos Robson A S 
Published: November 2023

Aerobic exercise training attenuates asthma‐induced airway inflammation, pulmonary remodelling and bronchial hyperresponsiveness. In addition, aerobic exercise increase circulating and tissue levels of angiotensin‐(1–7) [Ang‐(1–7)], which was shown to attenuate inflammation in different diseases. In the present study, we evaluated whether Ang‐(1–7) is involved in the beneficial effects of aerobic training in an experimental model of chronic allergic lung inflammation (asthma). BALB/c mice were subjected to a chronic protocol of asthma induced by ovalbumine (OVA) immunization (4 i.p. injections of OVA 14 days apart) and sensitization (OVA inhalation, 3 times a week during 4 weeks). Simultaneously to sensitization period, part of the animals were treated with the antagonist of Ang‐(1–7) receptor Mas (A779, 1μg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1h/day, 5 days/week during 4 weeks). Non‐asthmatic and sedentary mice (controls) received saline i.p. and inhalation with saline at same time points of experimental groups. The serum IgE levels were determined by ELISA, the airway remodelling by histology, infiltration of inflammatory cells in the lung by enzymatic activity assay. The gene expression of PGC‐1α was determined by qRT‐PCR and the protein expression of fibronectin in the lung by Western blotting. Treatment of asthmatic and trained animals with A779 prevented: i) the reduction in serum IgE levels (23±10 U/ml vs 0±0 U/ml in OVA‐TRE); ii) the reduction in extracellular matrix deposition in the airways (32±1% vs 17±2% in OVA‐TRE); iii) the reduction in the alveolar wall thickening (3±0.3 μm2 vs 1.8±0.1 μm2 in OVA‐TRE); iv) the reduction in MPO enzyme activity (neutrophils infiltration; 1.51±0.11 D.O./mg vs 1.01±0.06 D.O./mg in OVA‐TRE); v) the decrease in protein expression of fibronectin in the lung. Physical training was confirmed by the increase in PGC1‐α in OVA‐TRE (1.85±0.14 a.u.) and OVA‐TRE‐A779 (1.62±0.48 a.u.) in comparison to sedentary animals (0.96±0.15 a.u.). These data suggest that Mas receptor activation is involved, at least in part, in the anti‐inflammatory and anti‐fibrotic effect of aerobic training in animals subjected to an experimental model of chronic pulmonary lung inflammation. FINNANCIAL SUPPORT: FAPEMIG, CAPES, CNPq, INCT‐NanobiofarSupport or Funding InformationFAPEMIG, CAPES, CNPq, INCT‐Nanobiofar
Interaction between Chronic Intermittent Hypoxia and Aging in the Lung Tissue
Authors: Brinkman Jacqueline , Torres Marta , Broytman Oleg , Farre Ramon , Almendros Isaac , Teodorescu Mihaela 
Published: November 2023

RationaleAging is a powerful risk factor for obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), a key feature of OSA has been shown to lead to heterogeneous lung remodeling in rats, consisting of airways fibrosis and peripheral emphysema‐like formations. In humans, it is also known that with aging lung function declines, in part due to senile emphysema. Emphysema is caused by enhanced synthesis of matrix metalloproteinases (MMPs) by alternatively activated (M2‐polarized) macrophages and aberrant expression of neutrophil elastase (NE), a protease that destroys host tissue. The objective of this study is to examine the molecular interactions of aging and CIH in a mouse model.MethodsWild type C57BL/6j, female mice (n=3–4/group), aged 4 months (young) and 23 months (old) were exposed to either CIH, defined as 60 events per hour (40 seconds 20% O2 and 20 seconds 5% O2), for 6 hours per day, or normoxia (Nx), for 8 weeks. Mouse lungs were excised, frozen at −80 C, and analyzed for macrophage scavenger receptor (MSR1), a macrophage marker and NE by western blot. Total protein was resolved by SDS‐PAGE. Images were quantified by densitometry using ImageJ software.ResultsProtein levels of MSR1 (Figure 1A): 1) in the 4/CIH group was significantly higher than in the 4/Nx and comparable to 23/Nx group. NE protein levels (Figure 1B): 1) were highest in the 23/CIH and significantly different from 23/Nx group (p<0.05); 2) appeared to be comparable between 4/CIH and 23/Nx groups.ConclusionsLungs exposed to CIH have increased MSR1 protein expression to levels comparable to that of aged lungs; aging amplified the effects of CIH on NE levels. These results suggest that CIH leads to accelerated aging in the lung; various pathways may be more or less expressed.Support or Funding InformationDepartment of Medicine Pilot Funds
Effects of Chronic Intermittent Hypoxia (CIH) on mTORC Signaling in the Lung
Authors: Brinkman Jacqueline , Torres Marta , Broytman Oleg , Farre Ramon , Almendros Isaac , Lamming Dudley , Teodorescu Mihaela 
Published: November 2023

RationaleThe mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine protein kinase that promotes anabolic processes (protein translation, lipogenesis and nucleotide syntheses) and limits catabolic processes, such as autophagy; thus, modulates senesce in various tissues. S6K1 and its downstream targets SKAR and S6 substrate are involved in mTORC1 signaling, whereas 4EB‐P1 is an inhibitory regulator of mTORC1‐induced protein translation. Chronic intermittent hypoxia (CIH)—the hallmark feature of sleep apnea, leads to heterogeneous remodeling in the lung, similar to “senile remodeling” (senile emphysema and fibrosis). However, whether CIH modulates the mTORC1 pathway to underlie these processes remains unknown. We hypothesized that CIH leads to downregulation of mTORC1 signaling, contributing to accelerated aging in the lung.MethodsWild type C57BL/6j, female mice (n=3–4/group), aged 4 months (young) and 23 months (old) were exposed to either CIH, defined as 60 events per hour (40 seconds 20% O2 and 20 seconds 5% O2), for 6 hours per day, or normoxia (Nx), for 8 weeks. Mouse lungs were excised, frozen at −80 C, and analyzed for phosphorylated (P) S6K, S6 and 4EB‐P1 protein levels by Western blot. Total protein was resolved by SDS‐PAGE. Images were quantified by densitometry using ImageJ software. Data were expressed as ratio of phosphorylated component/total protein.ResultsP‐S6K levels (Figure 1A): 1) in the 4/CIH group was significantly lower than in the 4/Nx and comparable to 23/Nx group; 2) in the 23/CIH group trended to be lower than in the 23/Nx. There were no group differences in PS6 levels (p=0.92). Meanwhile, phosphorylated 4E‐BP1 levels (Figure 1B): 1) in the 4/CIH group were higher than in 4/Nx and comparable to 23/Nx group; 2) whereas, in the 23/CIH tended to be higher than the 23/Nx group.ConclusionsLungs exposed to CIH demonstrate reduced downstream mTORC1 P‐S6K signaling, concurrent with increased levels of the inhibitory regulator of mTORC1‐induced protein translation, 4E‐BP1; aging may amplify these effects. These results suggest that CIH could lead to reduced mTOR‐induced protein synthesis and accelerated aging in the lung.Support or Funding InformationSchool of Medicine Pilot funds
Sex differences in the role of urothelium in rat bladder contractile function
Authors: Szasz Theodora , Burgess Beth , Webb R. Clinton 
Published: November 2023

Bladder dysfunction is a prevalent condition associated with diabetes, aging, and cardiovascular disease. Despite sex differences in the risk factors, clinical findings and prevalence of diseases associated with bladder dysfunction, the role of sex differences in the physiological regulation of bladder function has been poorly investigated. We have previously observed that contractile responses to both carbachol (CCh) and electrical field stimulation (EFS) were greater in the male than the female rat bladder segments in both the presence and absence of urothelium. We hypothesized that sex differences in the role of urothelium in bladder contraction may underlie the sex differences observed clinically in bladder dysfunction. Female and male rat bladder contractile responses to CCh were measured in the presence and absence of the cyclooxygenase (COX) inhibitor indomethacin and the nitric oxide synthase (NOS) inhibitor L‐NAME, and in the presence and absence of urothelium. We observed that the presence of urothelium inhibited CCh‐induced contraction in the bladder, and this inhibitory effect was larger in the female than the male bladder (ΔEmax CCh[−Uro +Uro] (mN/mg) female=1.38±0.58, male=0.53±0.31). Incubation of bladder segments with indomethacin reverted the inhibitory effect of urothelium on CCh‐induced contraction in the male, but not the female bladder. Incubation of bladder segments with both indomethacin and L‐NAME reverted the inhibitory effect of urothelium on CCh‐induced contraction in bladder segments from both sexes. Our data suggest that there are sex differences in the physiological contractile function of the rat bladder in basal conditions, and that the contribution of COX to urothelium‐mediated contractile mechanisms is greater in the male than the female.Support or Funding InformationNIDDK Diabetic Complications Consortium (DiaComp, www.diacomp.org), grant DK076169.
Sex differences in molecular mechanisms of vascular aging
Authors: DuPont Jennifer , Davel Ana , McCarthy Joseph , Aronovitz Mark , Baur Wendy , Jaffe Iris 
Published: November 2023

Hypertension (HTN) is the most prevalent cardiovascular disease risk factor. Although HTN incidence rises profoundly with age in both sexes, females are relatively protected when they are young and after menopause, females ultimately exceed males in the incidence and adverse outcomes of HTN. In male mice with SMC‐specific deletion of the mineralocorticoid receptor (MR‐KO), we showed protection from the aging‐associated rise in blood pressure (BP). We show that in males, the mechanism involves SMC‐MR transcriptionally repressing vascular miR‐155 expression with age, which then promotes an increase in expression of miR‐155 target genes, Cav1.2, the pore‐forming subunit of the L‐type calcium channel (LTCC) and the angiotensin II type 1 receptor (AT1R). Further studies revealed that restoration of SMC‐specific miR‐155 rescues the aging phenotype observed in male mice. Specifically, raising SMC‐miR‐155 expression resulted in decreased Cav1.2 and AT1R expression and LTCC‐and AT1R‐mediated vasoconstriction. In female mice, however, Cav1.2 and AT1R expression did not change with age. Additionally, vasoconstriction to LTCC agonist BayK‐8644 and Ang II are not increased in aging females compared to young females. These results suggest that mechanism of vascular aging and BP control are distinct between males and females. These data support that sex‐specific therapies may be beneficial in managing vascular aging and BP control.Support or Funding InformationSupported by HL095590‐05, HL119290, and 15POST21300000.
Constructing 3 Dimensional Models of Sensory and Motor Tracts of the Spinal Cord as an Active Learning Technique
Authors: Knight Sarah 
Published: November 2023

The aim of this study was to measure the effectiveness of making 3 dimensional models as a method to enhance student understanding, enthusiasm and retention of the anatomy and physiology of pathways of the spinal cord. A total of 20 students participated in this study and were enrolled in a two semester undergraduate Human Anatomy and Physiology course taught at American University.Students worked in self‐selected groups of between 5–7 students. Following a lecture on the motor and sensory tracts of the spinal cord as part of the nervous system module, students were given the task of constructing 3 dimensional models of a number of pathways in order to visualize the different neural pathways in relation to each other in a hands‐on manner. Students were responsible for constructing models of a list of pathways of the spinal cord from colored card and ribbon. Pieces of card represented cerebrum, cerebellum, medulla and spinal cord and ribbon was used to trace the pathways. Students constructed and labelled multiple pathways on each model. The students were able to use their notes and text book as reference material while constructing the models. Upon completion of the task we reviewed the models as a class for 5–10 minutes and students had the opportunity to correct any errors and misunderstandings. Students completed an anonymous questionnaire in order to obtain feedback on the effectiveness of the model making exercise and the students experience.Of the 20 students polled 60% agreed or strongly agreed with the statement that the exercise increased their learning of the topic. At least 85% of participants agreed or strongly agreed that working as part of a group was beneficial in this exercise. More than 60% of the students polled reported that the time spent on the exercise was sufficient. However, in the written feedback from students 50% requested more time for discussion after the exercise. Other comments included preferring smaller working groups and more discussion time before the exercise.One drawback from this study was the absence of a control group of students that didn't participate in the model making exercise. This therefore prevented comparison of how the model making task affected student learning.In conclusion the results indicate that the students reported a perceived benefit from the model making exercise however adjustments such as increasing discussion time afterwards and using smaller working groups of students may improve the outcomes of this exercise.
Learning phundamental physiology with phUn Augusta scientists
Authors: Irsik Debra L , Abdul Yasir , Ferreira Neto Hildebrando C. , Choudhary Vivek , Crislip Ryan , Gillis Ellen , Klee Nicole S. , Quinones Patricia Martinez , McCarthy Cameron G. , Payne Anthony , Szasz Theodora , Valenzuela John Paul 
Published: November 2023

The American Physiological Society sponsors Physiology Understanding Week to excite children about careers in science. Augusta University physiologists held events at 3 local schools, using programs created to appeal to different age groups.The first program was geared toward 7th graders. After an introduction to physiology and careers in science, 100 students rotated through 5 different stations. They used a microscope to observe the eye, brain, lung and kidney histology. A fixed cow heart and anatomical models served to explain the structure and function of the heart, kidney and lung. Students learned about the cardiovascular system by measuring blood pressure changes after isometric contractions and by observing heart rate increases after a stressful activity. Finally, students tested their skills in a laparoscopic surgery teaching unit.The second program was designed to teach simpler scientific concepts to 140 4th and 5th graders. Students measured their lung capacity. They also learned about nutrition by measuring the salt and sugar content in different foods. Other concepts, such as the GI and renal function, the role of mucus, and the spread of infection through sneezing were also explored.Classes ended with a question and answer session, distribution of PhUN week bags, and a group photo. The students and teachers enjoyed interactive learning of physiology.