bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Ih to Postnatal Maturation of Muscarinic Modulation of Inspiratory Bursting at Hypoglossal Motoneurons in Neonatal Mice
Authors: Osbourne Alexis , Lee Chris , Revill Ann
Published: May 2024

Activation of hypoglossal motoneurons (XII MNs) contributes to stiffening of the upper airway during inspiration. The magnitude of this excitation is decreased during sleep, likely due to a combination of withdrawal of noradrenaline and acetylcholine release at XII MNs. Acetylcholine acts at muscarinic acetylcholine receptors (mAChRs) and surprisingly mAChR activation has an excitatory effect on inspiratory bursting in neonatal preparations, which becomes inhibitory in adult preparations. mAChRs modulate several ion channels and characterizing muscarinic effect changes at the XII nucleus will help to explain the mechanism of the inhibitory shift over postnatal maturation. The hyperpolarization activated cyclic nucleotide gated (HCN) channel is positively modulated by mAChRs. HCN channels give rise to Ih, a mixed cation current activated at hyperpolarized membrane potentials that contribute to membrane depolarization. Ihincreases dramatically with postnatal maturation in XII MNs. Thus, we hypothesize that 1) the effects of muscarinic modulation of Ih increases with postnatal maturation, and 2) that muscarinic activation of Ih contributes to the net inhibitory component of muscarinic modulation of inspiratory bursting at XII motoneurons. To test our hypotheses, we used the rhythmic medullary slice preparation to test the functional effects of muscarinic modulation of Ih on inspiratory bursting in neonatal CD1 mice (postnatal day, P0-P4) in combination with pharmacological block of Ih with ZD7288 (25 μM, 150s). Local application of muscarine (100μM, 30s) in the XII motor nucleus increased inspiratory burst amplitude (189 ± 58% of baseline, n = 9). Contrary to our hypothesis, there was no statistically significant difference between inspiratory burst amplitude elicited by muscarine in the presence of ZD7288 (192 ± 47% of baseline, n = 9) versus with the aCSF vehicle control (174 ± 43% of baseline, p = 0.098). We next tested a higher ZD7288 concentration (100 μM) and longer application times (150s, 330s) in neonatal preparations. Preliminary data (n=2) indicate that ZD7288 may increase muscarinic potentiation of inspiratory burst amplitude at XII MNs (muscarinic potentiation (100μM, 30s): control — 112 ±65 % of baseline, aCSF vehicle control - 131 ± 38% of baseline; ZD7288 100μM, 150s - 148 ± 44% of baseline; ZD7288 100μM, 330s - 107 ± 72% of baseline). Future research will elucidate whether the Ih contribution to muscarinic modulation of inspiratory bursting increases with postnatal maturation.

This is the full abstract presented at the American Physiology Summit 2024 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.
Adrenal circadian clock protein BMAL1 regulates aldosterone and renal excretory function in a sex- and time-dependent manner
Authors: Costello Hannah , Crislip G. Ryan , Cheng Kit-Yan , Mckee Annalisse , Mendez Victor , Douma Lauren , Gumz Michelle
Published: May 2024

BMAL1 is a core circadian clock protein that is important for circadian rhythms of physiological function, as well as maintaining physiological homeostasis, including aspects of kidney function. Global Bmal1 knockout (KO) male mice exhibit loss of diurnal rhythm of renal sodium (Na) excretion in response to a normal or high salt diet. However, renal Na excretion rhythm remained intact in kidney-specific Bmal1 KO male mice. The adrenal gland synthesizes hormones, such as aldosterone, which influence renal electrolyte handling. The role of adrenal BMAL1 in the regulation of renal function remains unknown. The study objective was to test the hypothesis that adrenal BMAL1 is required for normal rhythms of aldosterone and renal Na handling. Male and female adrenal-specific aldosterone synthase Cre positive (AS) Bmal1 KO and littermate Cre negative, floxed control mice ( n=5-9/genotype) were acclimated to metabolic cages for 3 days then samples were collected for three days with mice on a normal salt diet followed by 7 days on a low salt diet to challenge the mice to stimulate aldosterone production. Twelve-hour food intake was measured, and urine samples were collected to measure night/day patterns in renal Na balance. Urinary aldosterone excretion was measured by ELISA. Both day and night urinary aldosterone excretion were increased following a low salt diet in control and KO male mice (ANOVA main effect of diet, p<0.05). Male AS Bmal1 KO mice displayed a significant increase in day urinary aldosterone excretion following a normal and low salt diet (ANOVA main effect of genotype, p=0.0230), with a trend for an increase in night urinary aldosterone excretion ( p=0.0571). Interestingly, these genotype effects were not seen in female AS Bmal1 KO mice. Urinary aldosterone was increased following a low salt diet in female mice, but only during the nighttime in control and KO mice ( p=0.0205). Sex differences were also observed in renal Na balance, where Na balance was more positive during the day in male, but not female, AS Bmal1 KO vs. control mice (ANOVA main effect of genotype, p=0.0282). Together, these data suggest adrenal BMAL1 is required for normal rhythms of aldosterone and renal Na balance in a sex-dependent manner. Future work will investigate whether the changes in aldosterone contribute to changes in renal Na balance.

This work was supported by the American Heart Association (Postdoctoral FellowshipP0240441 to H.C.; Established Investigator Award 19EIA34660135 to M.G), theRobert and Mary Cade Professorship in Physiology (to M.G.) and the NIH(F32DK121424 to G.R.C.).

This is the full abstract presented at the American Physiology Summit 2024 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 hemoglobin-O2 affnity on aerobic capacity in deer mice
Authors: Garvey Kayla , Scott Graham
Published: May 2024

High-altitude hypoxia can constrain tissue O2 supply, and several high-altitude populations and species have evolved adaptations to overcome this challenge. Evolved increases in hemoglobin-O2 (Hb-O2) affnity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity (maximal O2 consumption) in hypoxia remains contentious. The influence of Hb-O2 affnity on aerobic capacity in hypoxia could vary depending on other traits in the O2 transport pathway, but this possibility is poorly understood. We examined this issue in deer mice ( Peromyscus maniculatus), which is found from sea level to >4300m altitude in the Rocky Mountains. Mice from populations native to high altitude and low altitude were born and raised to adulthood in captivity. Low-altitude mice (n=14) were acclimated to warm (25°C) normoxia, and high-altitude mice (n=14) were acclimated to cold (5°C) hypoxia (~12 kPa O2) for 6 weeks, creating two groups with very different capacities for O2 transport in hypoxia. Aerobic capacity for thermogenesis (VO2max) was then measured in hypoxia after each of three pharmacological treatments to manipulate Hb-O2 affnity: saline (control); efaproxiral, a negative allosteric regulator that decreases Hb-O2 affnity; and sodium cyanate, which covalently modifies Hb and increases Hb-O2 affnity. In control conditions, high-altitude mice had higher VO2max and arterial O2 saturation (SaO2) in hypoxia and higher Hb-O2 affnity (lower P50) than low-altitude mice. Efaproxiral reduced SaO2 and led to similar decreases in VO2max in both populations. Sodium cyanate increased SaO2 in hypoxia in both populations. However, this was only associated with an increase in VO2max in 7 of 14 high-altitude mice and 4 of 14 low-altitude mice. Our results suggest that Hb-O2 affnity may be optimal for aerobic capacity in hypoxia in high-altitude mice, and that reductions in Hb-O2 affnity reduce performance.

Supported by NSERC of Canada.

This is the full abstract presented at the American Physiology Summit 2024 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.
Aging Reduces Cardiac Contractility by Altering Cardiac Regulatory and Contractile Proteins
Authors: Han Young , Pakkam Madona , Sieck Gary , Brozovich Frank
Published: May 2024

Aging is associated with an increased incidence of cardiac dysfunction. We hypothesized that aging associated changes in cardiac regulatory and contractile proteins produce contractile dysfunction. We assessed regulatory and contractile protein expression as well as contractility in left ventricular cardiac muscle from Fischer F-344 rats at 6-, 18-, and 24-month of age. Age-related changes in the expression of β-MHC as well as the expression and phosphorylation of troponin I (TnI) and cardiac myosin binding C protein (MyBP-C) were assessed by Western blot. Aging was associated with an increase in the expression of β-MHC and the phosphorylation of both TnI at Ser23/24 and MyBP-C. Mechanical properties were assessed in Triton-X permeabilized anterior papillary muscle from the left ventricle from both 6- and 24-month old rats. In papillary muscle of 24-month old rats, there was a decrease in maximum Ca2+ activated force, Ca2+ sensitivity of force and the rate constant for force recovery after quick release (ktr). Additionally, cardiomyocytes were isolated from the left ventricle at 6-, 18-, and 24-month of age using a modified Langendorff system. Cardiomyocytes were then loaded with fura-2 AM to measure cytosolic calcium ([Ca2+]cyt) responses to electrical field stimulation (0.5 Hz). [Ca2+]cyt and contractile (sarcomere length shortening) responses to stimulation were simultaneously measured using an IonOptix system. In older cardiomyocytes, the amplitude of evoked [Ca2+]cyt responses was reduced while there was no difference in the kinetics of the [Ca2+]cyt transient. The extent of sarcomere length shortening as well as the rates of both shortening and relaxation were reduced. These results demonstrate that aging is associated with changes in the expression and phosphorylation of contractile and regulatory proteins, which produce changes in cardiac contractility.

Supported by a Mayo CV Prospective Grant (FVB).

This is the full abstract presented at the American Physiology Summit 2024 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.
Endothelial cell HDAC1 mediates aortic stiffness in diet-induced obese mice
Authors: Edell Claudia , Colson Jackson , Dunaway Luke , Allan J. Miller , Kellum Cailin , Walker Savannah , Pati Paramita
Published: May 2024

Histone deacetylase 1 (HDAC1) is an important regulator of cell differentiation and is associated with progression of cardiovascular disease (CVD). Our lab previously showed that over-expression of HDAC1 in cultured endothelial cells reduces NO production. Other investigators have shown increased HDAC1 protein in models of CVD. However, there is a gap in knowledge of whether endothelial-specific HDAC1 mediates vascular dysfunction in models of CVD. Diet induced obesity (DIO) is a leading risk factor for CVD, thus our studies are focused on a chronic high fat feeding mouse model. Our studies utilize a mouse model of DIO where mice are fed a normal diet (ND, 10% fat) or high fat diet (DIO, 45% fat) beginning at 8 weeks of age for 20 weeks. Previously, we showed that this model of DIO in male mice significantly increases aortic stiffness (measured by pulse wave velocity, PWV) and increases aortic thickness compared to ND (PWV: unpaired T test, n=9-12, normal diet (ND) vs DIO, p=<0.0001; Aortic Thickness: unpaired T test, n=6, ND vs DIO, p=0.005). We hypothesized that endothelial-specific HDAC1 mediates aortic dysfunction in a mouse model of DIO. We generated inducible endothelial-Scl-Cre-ER-HDAC1 knockout (KO) mice (iEC-HDAC1KO), which specifically deletes HDAC1 in endothelial cells after tamoxifen injection, and the flox control mice (iEC-HDAC1flox), which does not delete HDAC1 after tamoxifen injection. We assessed aortic stiffness of iEC-HDAC1 KO and iEC-HDAC1flox in ND and DIO mice. We treated with tamoxifen for 5 days when ND mice were 20 weeks old and measured PWV 2 weeks later. Interestingly, iEC-HDAC1KO mice had significantly reduced PWV compared to iEC-HDAC1flox mice on ND (unpaired T test; n=4-5, p=0.009). At week 18 of the DIO protocol, mice were given daily tamoxifen injections for 5 days. After week 20 of the DIO protocol, iEC-HDAC1KO DIO mice had significantly reduced PWV compared to iEC-HDAC1flox DIO mice (unpaired T test; n=4-5; p=0.008). These data indicate that endothelial-specific HDAC1 mediates vascular stiffness and remodeling in high fat fed mice. Further investigation is needed to understand the relationship of endothelial HDAC1 and NO in the context of DIO and aortic health.

Funding: R01 DK134562, F31HL167626.

This is the full abstract presented at the American Physiology Summit 2024 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.
Modeling and Analysis of Central and Peripheral Autonomic Contributions to Decreased Cardiac Vagal Tone Following Myocardial Infarction
Authors: Gee Michelle , Lenhoff Abraham , Schwaber James , Vadigepalli Rajanikanth
Published: May 2024

Loss of cardiac function following myocardial infarction is accompanied by neural adaptation in baroreflex systems that are compensatory in the short term but then become associated with long-term disease progression. A hallmark of these baroreflex changes is decreased vagal tone. The closed-loop feedback structure of the baroreflexes confounds the source of decreased vagal tone following myocardial infarction (MI). We recognize that in a feedback network causality is distributed in the network interactions, and so explore the effects of MI on the potential contribution to vagal withdrawal of each neural component of our previously published closed-loop baroreflex computational model. The model is composed of differential equations representing the blood flow through various body compartments and sigmoidal functions to represent the saturating firing behavior of neurons. Neuronal adaptations leading to decreased vagal activity could occur in various neuronal groups located centrally in the brainstem. Adaptations could also occur peripherally at the baroreceptors or the heart’s “little brain”, the intrinsic cardiac nervous system. We developed five alternative models to reflect these hypotheses. Of the alternative models, only the model representing adaptation in the baroreceptors predicted both physiological baroreflex function and a decrease in vagus nerve activity. These findings suggest that decreased vagal activity after myocardial ischemia may be due, at least in part, to a decrease in baroreceptor sensitivity. We also link these model predictions with experimental evidence from the literature.

NIH U01-HL133360, NIH OT2-OD030534, NSF 1940700, and NSF OAC-1919839.

This is the full abstract presented at the American Physiology Summit 2024 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.
CHARACTERIZATION OF THE ROLE OF ESTROGEN RECEPTORS IN EXACERBATING AIRWAY HYPERRESPONSIVENESS
Authors: Ekpruke Carolyn , Rousselle Dustin , Babayev Maksat , Sharma Shikha , Silveyra Patricia
Published: May 2024

Clinical, animal, and epidemiological studies have suggested a higher prevalence of asthma in women than in men, implicating the sex steroids, most importantly, the estrogen in the lungs, as a key player. Estrogen is known to act through its alpha and beta receptors located on the lungs and several researchers have reported that they play a differential role in asthma. In this study, we evaluated the receptor-specific effect of estrogen in mediating Airway Hyperresponsiveness (AHR) using the estrogen receptors knock-out mice (Esr α KO and Esr β KO). Adult (8-10 weeks old) male and female C57BL/6J (WT), Esr α KO, and Esr β KO mice (n=2/8 per group) were challenged with 50 μl of House Dust Mite (HDM) solution (25 μg of HDM extract derived from two species, Dermatophagoides pteronyssinus and Dermatophagoides farinae) or vehicle (phosphate-buffered saline, PBS) intranasally for 5 weeks. At 72 hours after the last exposure, AHR was assessed through the Methacholine challenge (MCh) of varying doses (0, 3.13, 12.5, 25, 50, 100 mg/mL) using the flexiVent rodent ventilator system (SCIREQ) and immediately followed by the collection of bronchoalveolar lavage fluid (BALF) for the preparation of cytospin slides to analyze immune cells. Data analysis was done using GraphPad Prism 10.0.3, and the P-value < 0.05 was considered significant. Resistance (Rrs), Elastance (Ers), Conducting airway resistance (Rn), Tissue resistance (G), and Tissue elastance (H) were significantly increased ( P < 0.05) in male and female Esr β KO induced with HDM compared to PBS. Interestingly, Esr α KO HDM-induced mice showed a significant reduction in AHR only in the males and not the females, whereas it was not significantly different in the WT (males and females) exposed to HDM or PBS-induced. However, we observed that there was no statistically significant difference at P- value < 0.05 in the macrophage and lymphocyte count in the HDM-induced mice compared to the PBS in the estrogen receptor knockout mice and the WT. Eosinophil and neutrophil recruitments were observed in all the estrogen receptor knock-out groups exposed to HDM compared to the PBS but not in the WT, however, they were prominent in the Esr β KO but were not significant at P- value < 0.05. In conclusion, Esr β KO mice (males and females) showed declined lung function after exposure to allergens, indicating that Esr β plays an important role in AHR and understanding the mechanisms involved would help to develop novel therapeutics for the treatment of allergic airway inflammation in females.

This study was supported by the National Heart Lung and Blood Institute: R01HL159764 (PS) and R03HL141618 (PS).

This is the full abstract presented at the American Physiology Summit 2024 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.
Comparison of Online and Onsite Student Learning of Physiology Core Concepts
Authors: Tamarkin Dawn , Aleshire David , Salimi Nima , Deryugina Elena , Zareitalabad Parva
Published: May 2024

We have recently introduced the physiology Core Concepts into our introductory anatomy and physiology lecture classes, both online and onsite. In each of two sequential terms of anatomy and physiology our students are working through disease descriptions to learn about the Core Concepts. Both online and onsite classes are using common disease descriptions, although they are being deployed in different manners in the two formats; the disease descriptions are embedded in the discussion boards for online classes while they are used for groupwork and discussion in onsite classes. The students in both formats of these courses are also being evaluated using the same set of assessment questions. A comparison between the two formats of the understanding of the Core Concepts as demonstrated through the assessments, as well as information on challenges and successes in deploying this strategy with our nontraditional students, is provided.

A Howard Hughes Medical Institute Inclusive Excellence 3 Award enables our part-time faculty to travel to the American Physiology Summit.

This is the full abstract presented at the American Physiology Summit 2024 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.
Acute Intermittent Hypoxia with Hypercapnia has Complex effects on Phrenic Long-Term Facilitation that Depend on Delivery in the Rest versus Active Phase in Rats
Authors: L.E. Butenas Alec , B. Marciante Alexandria , Burrowes Kayla , S. Mitchell Gordon
Published: May 2024

Exploration of mechanisms giving rise to respiratory motor plasticity, such as phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH), has inspired new therapeutic approaches to treat individuals affected by conditions such as spinal cord injury or other clinical disorders. One key step in the translation between rodent models and humans is the apparent need for hypercapnia (either baseline or within hypoxic episodes) during AIH. Whereas AIH consisting of 15, 1-minute hypoxic episodes (1-minute intervals) elicits robust pLTF in rats, similar protocols have minimal impact in humans—unless PaCO2 levels are increased. Although prior studies report that elevated baseline CO2 actually impairs AIH-induced pLTF in rats, the impact of hypercapnia within hypoxic episodes is not known. Thus, we compared AIH with and without concurrent hypercapnia (AIH versus AIHH) on pLTF in anesthetized rats. Since our laboratory recently reported profound time-of-day effects on pLTF magnitude and/or mechanisms, we also compared AIH versus AIHH-induced pLTF during the daily rest and active phase. We hypothesized that AIHH would enhance pLTF versus AIH in both phases, suggesting it may be a more effective intervention to elicit respiratory motor plasticity and respiratory rehabilitation. pLTF was assessed in anesthetized, paralyzed, vagotomized and ventilated male Sprague-Dawley rats ( n=6 per group) exposed to moderate AIH (arterial PO2 = 40-55mmHg) consisting of: 1) 15, 1-minute hypoxic episodes with concurrent hypercapnia (arterial PCO2 ~50mmHg) or 15, 1-minute episodes of isocapnic hypoxia (baseline arterial PCO2 ~2 mmHg above the recruitment threshold; ~40-42 mmHg). We also compared AIHH versus AIH during the active phase using prior published data (AIHH, n = 4; AIH, n = 7; data from Nair et al., Function, 2023 and Marciante et al., Function, 2023, respectively). Contrary to our hypothesis, pLTF was attenuated 90 minutes post-AIHH (37±8%) versus AIH (83±4%; p<0.001) in the rest phase. In striking contrast, during the active phase, pLTF was greater with AIHH (60±11%) versus AIH (30±4%; P=0.012). These unexpected outcomes demonstrate that time of day (or the rest/active phase) must be considered before adding hypercapnia to an AIH protocol. Although the mechanisms of this difference remain unclear, our results make clear that there is still a great deal to learn about mechanisms of AIH-induced respiratory motor plasticity, including the complex interplay between hypoxia, hypercapnia and their impact on pLTF.

Supported by: NIH R01 HL147554 & R01 HL148030 (PI: G. Mitchell).

This is the full abstract presented at the American Physiology Summit 2024 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.
Establishing the SHort course In transFerable skills Training (SHIFT) Program
Authors: Woods Letha , Lindsey Merry
Published: May 2024

While Ph.D. programs prepare graduate students to perform biomedical research, a defined systematic training program for transferable skills is generally lacking. When provided, this training is often informal, unstructured, or inconsistent. Therefore, there is a need to provide critical skills in marketing, relationship building, project management, and budgeting to prepare trainees to navigate into a productive, engaging, and rewarding biomedical research career. To address this gap in training, the graduate school at Meharry Medical College has developed the SH ort Course I n trans F erable skills T raining (SHIFT) Program, a one-year professional development program accessible to graduate students in the Southeast United States. The SHIFT Program has been launched to equip trainees with skills essential for success in all biomedical science careers. PhD Students between years one and two in their graduate program will be taught the primary constituents of career management through the use of four training modules. In Module I, students will complete self-assessments and be assigned to a small peer-mentoring team of six students with two mentors. Module II will consist of a 5-day workshop that encompasses instruction on the transferable skills identified as essential for career success. Module III will entail monthly interactive discussions over a 6-month period involving case study review and mentor-guided discussions to further reinforce skills learned. In Module IV, students will compile the information learned from Modules I-III to develop an Individual Development Plan that incorporates 3-5 specific, measurable, attainable, relevant, and time-based (SMART) career goals. Collectively, the SHIFT Program will allow participants to train, practice, and refresh skills, empowering them to navigate career transitions and obtain success in the career of their choice.

NIH GM151274 and VA I01BX000505.

This is the full abstract presented at the American Physiology Summit 2024 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.
Recovery of Ventilatory and Metabolic Responses to Hypoxia after Chronic Hypoxia in Neonatal Rats
Authors: Kinnally Annie , Lee Darya , Bavis Ryan
Published: May 2024

Chronic hypoxia (CH) from birth blunts the hypoxic ventilatory response (HVR) in newborn rats, but there is conflicting evidence as to whether (or how quickly) the HVR recovers after these rats are returned to room air. In this study, Sprague-Dawley rats were exposed to either 21% O2 (Control) or 12% O2 (CH) for the first 3 postnatal days. Breathing and metabolism were studied using head-body plethysmography and respirometry immediately after the 3 days of CH (i.e., at P3) or after 1, 4-5, or 7 days of recovery in room air (i.e., at P4, P7-8, or P10). The early phase of the HVR was blunted in CH rats at P3 (13.7± 2.3 vs. 30.6±3.4 % increase from baseline during 12% O2), and the HVR was more biphasic in CH rats after 1 day of recovery. However, no significant differences in the HVR were observed between treatment groups after 3-4 or 7 days of recovery. Males and females showed similar patterns. Changes in ventilation during hypoxia were strongly biphasic in the younger age groups: ventilation increased initially, but this was followed by a gradual decline in ventilation towards or below baseline levels. However, when accounting for metabolic depression, all age groups continued to hyperventilate during the late phase of the HVR [i.e., the ratio of ventilation to CO2 production (CO2 convection requirement) remained elevated relative to baseline values]. The CO2 convection requirement response to hypoxia did not differ between treatment groups during the late phase of the HVR at any age, but metabolism and CO2 convection requirement could not be determined during the early phase of the HVR due to non-steady state conditions. In conclusion, 3 days of CH produces only a transient blunting of the HVR in newborn rats. Longer CH exposures may be required to elicit persistent changes in the HVR or, alternatively, this plasticity may not be revealed until after puberty.

Supported by NIH grant P20 GM-103423 (Maine INBRE).

This is the full abstract presented at the American Physiology Summit 2024 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.
Restoring Cardiac Health: Abstinence Leads to Recovery from Alcohol-Induced Cardiomyopathy
Authors: Edavettal Joshua , Harris Nicholas , Cohen Sarah , Paloczi Janos , Bysani Chandrasekar , Gardner Jason D.
Published: May 2024

Chronic drinking can lead to alcohol-induced cardiomyopathy (ACM), a disease currently without a cure. Using a mouse model of ACM, we observed significant cardiac dysfunction after 30 days. Our study’s goal was to investigate the potential restoration of cardiac function following a period of abstinence. Our hypothesis is that abstinence can lead to an observable recovery in overall cardiac function. C57BL/6J mice were given the Lieber-DeCarli liquid diet with 5% ethanol for 30 days, with two ethanol binges on days 10 and 30 (5 g/kg). After the 30-day ethanol exposure, the mice were transitioned to an ethanol-free diet for an additional 30 days. Left ventricular catheterization and echocardiography were conducted at the 30- and 60-day timepoints. 30 days of ethanol consumption led to significant decreases in both systolic and diastolic function. However, following a period of alcohol abstinence, there was a marked improvement. Specifically, the 30-day ethanol mice exhibited increases in stroke work and dP/dt max after 30 days of abstinence; stroke work increased from 1119 ± 89 mmHg*μL to 2032 ± 139 mmHg*μL (p < 0.0001), and dP/dt max increased from 8054 ± 664 mmHg/s to 11967 ± 449 mmHg/s (p < 0.001). Diastolic function also improved; dP/dt min from -7711 ± 561 mmHg/s to -10202 ± 594 (p < 0.01). We also found a significant increase in load-independent cardiac contractility, i.e. the slope of end systolic pressure volume relation: 6.89 ± 0.6 mmHg/μL to 10.59 ± 1.57 mmHg/μL (p < 0.05). In conclusion, abstinence after chronic ethanol exposure can lead to a restoration of cardiac function in C57BL/6J mice. This model parallels limited clinical data on abstinence and will allow us to study the underlying mechanisms responsible for the restoration of function.

R21AA029747 (JG, CB), F30AA030472 (JE).

This is the full abstract presented at the American Physiology Summit 2024 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.
Analysis of Lysine Metabolism in a Rat Model of Type 2 Diabetes Reveals Modulation of Endocytosis and Glucose Metabolism
Authors: Tan Yifan , Dissanayake Lashodya , Kravtsova Olha , Demir Fatih , Levchenko Vladislav , Staruschenko Alexander , Rinschen Markus
Published: May 2024

Lysine is an essential amino acid that serves as a building block for proteins and plays a role in metabolic processes. While a recent study provided evidence that lysine is beneficial for hypertension-associated kidney disease, possibly through inhibiting renal tubular reabsorption and forming new lysine conjugates, knowledge about the role of lysine in diabetic nephropathy (DN) is rudimentary. Therefore, the aim of the study was to investigate the role of lysine in kidney function in the setting of DN and its underlying mechanisms. We hypothesized that lysine may impact the kidneys in the following ways: 1) by mediating protein endocytosis in proximal tubules; 2) by altering protein abundance in the kidneys and other organs; and 3) by disrupting metabolic pathways through the formation of conjugates or degradation products. We investigated the effects of lysine on proximal tubule endocytosis and other organs using proteomic approaches and studied changes in lysine conjugates and metabolic products using targeted metabolomics. The results of urinary proteomics suggested that lysine’s impact on endocytosis may be associated with the inhibition of megalin and cubilin. Furthermore, lysine affected proteins related to glucose metabolism. Subsequently, we proceeded to investigate the influence of lysine on various organs in Type 2 Diabetic Nephropathy (T2DN) rats. Gene Ontology (GO) enrichment revealed that lysine exerts tissue-specific effects on different organs, with pathways enriched in the kidney including phagocytosis and enzyme inhibitor activity. Additionally, within the kidney, the lysine-treated group showed downregulation of glycolysis-related enzymes. The metabolomics results showed that lysine leads to a decrease in glucose and an increase in fructose 1,6-bisphosphate, while also resulting in an upregulation of related metabolites in the tricarboxylic acid cycle (TCA cycle). Our findings showed changes in the protein composition involved in lysine-mediated endocytosis and the impact of lysine on glucose metabolism enzymes and metabolites. The specific molecular mechanisms are still under investigation.

R01 DK135644 and I01 BX004024 (to AS).

This is the full abstract presented at the American Physiology Summit 2024 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.
A Prospective Study Evaluating Gender Differences of Serious Outcomes through Difficult Airway Physiological Score (DAPS) in the Emergency Department
Authors: Waheed Shahan , Jawed Rida , Raheem Ahmed , Iqbal Mian Asad
Published: May 2024

Introduction. Gender variation in critically ill adults after resuscitation is reported in many studies. However, this variation is not well established when evaluating the physiological instability in this population. This study aimed to prospectively evaluate the gender variation in serious outcomes by the difficult airway physiological score (DAPS) among critically ill patients requiring endotracheal intubation (ETI). Methods. This is a cohort study conducted from August 2021 to December 2022 in the emergency department of Aga Khan University. The prospective validity of the difficult airway physiological score was derived using retrospective data and includes 12 variables: sex, age, time of intubation, hypotension, respiratory distress, vomiting, shock index >0.9, pH < 7.3, fever, anticipated decline, Glasgow Coma Scale (GCS) < 15, and agitation. The serious outcomes were cardiac arrest, mortality (within 1 hour after intubation in emergency), hypotension (systolic blood pressure <90 mmHg), and oxygen desaturation (SpO2 < 92%). The difference between males and females was assessed using the chi-square test, and the association of gender and serious outcomes was explored using Cox and logistic regression analysis. ROC curve analysis and area under the curve assessed score validity separately in males and females with serious outcomes. Results. We enrolled 326 patients with a mean age of 50.3 (±17.8), with 123 (33.7%) females and 203 (62.2%) males. 198 (60.7%) patients were >45 years old, of which 136 (67%) were male and 62 (50.4%) female. Cardiac arrest was observed in 56 (17.2%), with 24 (19.5%) females and 32 (15.8%) males, p value 0.348. Hypotension after intubation was observed in 132 (40.5%) patients, 56 (45.5%) females and 76 (37.4%) males, p value 0.149. Oxygen saturation (<92%) was observed in 80 (24.5%) patients, 32 (26%) females and 48 (23.6%) males, p value 0.630. In females, the DAPS of 11 had an area under the curve of 0.863 (0.74–0.91). The sensitivity of the score was 84.8%, the specificity was 71.9%, the PPV was 77.8%, and the NPV was 80.4% with an accuracy of 78.9%. In males, the DAPS score of 14 had an area under the curve of 0.892 (0.57–0.75). The sensitivity of the score was 67%, the specificity 93.8%, the PPV 92.2%, and the NPV 72.2% with an accuracy of 79.8%. Conclusions. The Difficult Airway Physiological Score (DAPS) predicts the risk of serious outcomes after intubation with high precision and reliability with different score cutoffs between the two sexes, highlighting the gender variation of a difficult airway.
Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes
Authors: Huang Dongni , Ran Yuxin , Chen Ruixin , He Jie , Yin Nanlin , Qi Hongbo
Published: May 2024

Premature rupture of membrane (PROM) refers to the rupture of membranes before the onset of labor which increases the risk of perinatal morbidity and mortality. Recently, circular RNAs (circRNAs) have emerged as promising regulators of diverse diseases. However, the circRNA expression profiles and potential circRNA–miRNA–mRNA regulatory mechanisms in PROM remain enigmatic. In this study, we displayed the expression profiles of circRNAs and mRNAs in plasma and fetal membranes of PROM and normal control (NC) groups based on circRNA microarray, the Gene Expression Omnibus database, and NCBI’s Sequence Read Archive. A total of 1,459 differentially expressed circRNAs (DECs) in PROM were identified, with 406 upregulated and 1,053 downregulated. Then, we constructed the circRNA–miRNA–mRNA network in PROM, encompassing 22 circRNA–miRNA pairs and 128 miRNA–mRNA pairs. Based on the analysis of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene set enrichment analysis (GSEA), DECs were implicated in immune‐related pathways, with certain alterations persisting even postpartum. Notably, 11 host genes shared by DECs of fetal membrane tissue and prenatal plasma in PROM were significantly implicated in inflammatory processes and extracellular matrix regulation. Our results suggest that structurally stable circRNAs may predispose to PROM by mediating systemic immune imbalances, including peripheral leukocyte disorganization, local immune imbalance at the maternal–fetal interface, and local collagen disruption. This is the first time to decipher a landscape on circRNAs of PROM, reveals the pathogenic cause of PROM from the perspective of circRNA, and opens up a new direction for the diagnosis and treatment of PROM.
Biology, morphology and taxonomy of a snail-feeding leech from North Carolina, USA, provisionally identified as Helobdella lineata (Verrill, 1874) (Glossiphoniidae): First evidence for extra-oral digestion in the Hirudinea
Authors: SAWYER ROY T.
Published: May 2024

This is a twelve-year longitudinal study of a common snail-feeding leech indigenous to the Albemarle region of northeastern North Carolina, USA. Based on contents of this paper the species is provisionally identified as Helobdella lineata (Verrill, 1874). For all practical purposes this is the first comprehensive description of this species. Particular attention is focused on variability of its dorsal papillae and variable pigment patterns within the Albemarle population. A total of 404 specimens were collected from 25 collecting stations in disparate parts of the region. Specialised leech traps set in these swamps were monitored regularly yielding unprecedented information on its morphology, ecology and general biology. This study recognises four principal pigment variants within the Albemarle region which, based on dissections, appear to represent a single biological species. Moreover, limited observations suggest that pigment variability is attributable primarily to adaptive camouflage to local surroundings. Methodologically it is emphasized in this paper that variable traits cannot serve as key taxonomic anchors. A proposed alternative diagnosis for identifying H. lineata is based entirely on more rigorous, non-variable characters. A significant finding is that H. lineata is most meaningfully understood in terms of specialist adaptation to feeding on snails. Furthermore, it is proposed that such adaptation required a major evolutionary shift within the foregut of this species. Evidence is presented that H. lineata uses uniquely large salivary cells to dissolves solid snail tissue into a semi-fluid state before ingestion via a specialised proboscis. This is the first example of extra-oral digestion in the Hirudinea.
Two new species of the genus Plectiscus Gravenhorst, 1829 (Hymenoptera, Ichneumonidae: Orthocentrinae) from Kenya
Authors: VARGA OLEKSANDR
Published: May 2024

Two new orthocentrine species of the genus Plectiscus Gravenhorst, 1829, P. oblongus sp. n. and P. taitaensis sp. n., from Kenya are described and illustrated. An identification key to Afrotropical species of the genus is provided.
Two new species of Platynothrus and Heminothrus (Oribatida: Crotoniidae) from Mexico
Authors: VILLAGOMEZ FERNANDO , HEETHOFF MICHAEL
Published: May 2024

The oribatid mite genera Platynothrus and Heminothrus currently comprise 20 and 10 species, respectively, and collectively have a cosmopolitan distribution. They have been classified into three to five subgenera, depending on the classification. For Platynothrus, a couple of new species have been described in the last two years, while for Heminothrus, the last formal description of a new species was 26 years ago. In this study, we describe two new species of these crotoniid mites, discovered in the soil and litter of a tropical montane cloud forest in Mexico. One of these new species belongs to the genus Platynothrus, which can be distinguished from other species of this genus by the short clavate sensillus, curved smooth interlamellar seta, and the length of the notogastral setae. The second new species belongs to the genus Heminothrus, being characterized by a short rhomboidal sensillus and a very long interlamellar seta. Intraspecific genetic distances of the COX-1 mitochondrial marker were 2.15%, and 0.81% for the new Platynothrus and Heminothrus species, respectively.
A new species of Copidosoma Ratzeburg (Hymenoptera: Encyrtidae) parasitizing Neoleucinodes elegantalis (Guenée), N. imperialis (Guenée) and N. prophetica (Dyar) Capps (Lepidoptera: Crambidae) in Colombia and Ecuador
Authors: ÁVILA BLANCA IRENE VARGAS , MONTILLA ANA ELIZABETH DÍAZ
Published: May 2024

A new species of Copidosoma Ratzeburg, 1844 (Hymenoptera: Encyrtidae) from Colombia and Ecuador, Copidosoma takumasakondoi Vargas & Díaz, sp. nov., is described and illustrated based on the adult female and male. Copidosoma takumasakondoi was found parasitizing three species of nightshade fruit borers, i.e., Neoleucinodes elegantalis (Guenée), N. imperialis (Guenée) and N. prophetica (Dyar) Capps (Lepidoptera: Crambidae).
Description of the female of Heteragrion lencionii Vilela, Farias & Santos, 2021 (Odonata: Heteragrionidae), from Northeastern Brazil, with some ecological notes
Authors: FARIAS ANTONIO BRUNO SILVA , PEREIRA MARIA MIRELLY SANTIAGO , BARÃO KIM RIBEIRO , VILELA DIOGO SILVA , SANTOS JEAN CARLOS
Published: May 2024

Group A of the genus Heteragrion Selys, 1862 comprises 34 species, of which 19 have complete descriptions of females. The aim of this study was to describe the female Heteragrion lencionii Vilela, Farias & Santos, 2021 based on three specimens collected at the Federal Institute of Sergipe (Brazil, Sergipe, São Cristóvão, -10.9198, -37.1862, 30 m asl, A.B.S. Farias leg., UFS), including mating specimens. Here, we provide a detailed diagnosis and illustrations of the female, and compare it with its closest congeners. Heteragrion lencionii female is distinguished from others by the shape of the intersternite, shape of the posterior lobe of the prothorax, and coloration of the head. The distribution extensions are relevant because the species has not been recorded from the type locality since its original description.
Description of a new whitefly genus and two new species (Hemiptera: Aleyrodidae) from the Western Ghats and Andaman Islands, India
Authors: DUBEY ANIL KUMAR
Published: May 2024

Cerafilum gen. nov. is described for Cerafilum ochlandrae sp. nov. and Cerafilum saddlense sp. nov., from India and colonising bamboo species. Cerafilum gen. nov. is compared with the allied genus Aleuromarginatus Corbett and Setaleyrodes Takahashi and diagnoses and illustrations provided, including habitus, line drawings of holotype, diagnostic characteristics, types’ images and scanning electron microscope microphotographs.
New OTC Derivative Instrument for BRI Grand Strategy Integration: Case of ‘China, Mongolia and Russia’
Authors: Shichalina Valeriia A.
Published: May 2024

The Belt and Road Initiative is an economic integration plan. But at regional level, the financial capabilities of route countries do not allow the implementation of the Belt and Road. This is the need for and creation of a new financial form. This study aims to theoretically justify a new financial form for economic integration—new type of over-the-counter derivative financial instrument. This adaptation addresses the case of the transport corridor ‘China–Mongolia–Russia’ and ‘resident status’ of the Joint Economic Zone that will serve as a guarantee for the financial assets of the Belt and Road companies and increase their financial sustainability and investment revival in regions. In general, this has a positive effect on the development of the accounting system and increases the financial and investment interests of business participants, which can lead to new forms of entrepreneurial activity and become a catalyst for improving the welfare of regions of China–Mongolia–Russia transport corridor, and it is in line with the goals and investment initiatives of the Belt and Road project.
Impact of Trade Liberalisation and MSME Classification on Productivity of Indian Manufacturing Firms
Authors: Mukherjee Subhadip , Chanda Rupa
Published: May 2024

This article examines the effects of tariff and non-tariff reductions on firm-level productivity of large as well as Micro, Small and Medium Enterprises (MSMEs) in India’s manufacturing sector for the 1999–2009 period. We calculate input and final goods tariffs, effective rates of protection and non-tariff barriers (NTBs) for broad product groups using information from India’s Exim Policy of 1997–2003 and 2004–2009 to examine this impact. We use a balanced as well as unbalanced firm-level panel data set, while accounting for firm, industry, state and time-specific factors. By using fixed effect models and Heckman’s two-step estimation procedure, we find that trade liberalisation is associated with improved firm-level productivity for large firms but not in the case of MSMEs. We posit that this might be due to the relative disadvantages that Indian MSMEs face which prevent them from benefiting from trade liberalisation. We also find that productivity gains arising from the sourcing of imported inputs have been greater than those arising from increased product competition and that NTB liberalisation has had a greater impact compared to tariff liberalisation on firm-level productivity. Changes in MSME legislation and the classification of firms are also found to have a bearing on firm performance. Our study contributes to the literature by confirming the need to focus specifically on constraints faced by MSMEs if they are to benefit from trade liberalisation. It highlights the importance of liberalising trade in intermediates as well as the role of MSME classification in enabling productivity gains.

JEL Codes: L6, D24, L1, F13
Gandhian Ideas: His Days and Ours
Authors: Bhalla Priya
Published: May 2024

A large section of the world population continues to live in hunger, starvation, malnutrition, deplorable living conditions with unsafe drinking water, inadequate health amenities and lack of proper education. The fear and uncertainty associated with the COVID-19 pandemic have resulted in the loss of lives and livelihoods for a large number of poor and vulnerable persons, pushing them deeper into the confines of poverty. It is in times such as these that Gandhian thoughts are popularly invoked by Gandhi’s followers. The present study is an attempt to revisit the Gandhian perspective on the development of the Indian economy. It intends to capture and crystallise his socio-economic ideas on the wide expanse of issues in a comprehensive manner. These are systematically encapsulated in six Ends: employment, emancipation, equality and egalitarianism, environment, ethics and education. Further, the study goes on to discuss Gandhi’s economic prescriptions to achieve these six ends. Furthermore, it attempts to categorise the Gandhian methods into one of three states—alive, ailing or abandoned—based on their current usefulness. Additionally, if the status turns out to be failing or abandoned, it aims to provide a nearby current approach that can appropriately fit in Gandhi’s vision without being dismissed as being too far-fetched.