bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular and Intracellular Dehydration Affect Urinary Bladder Reactivity to Vasopressin and Neurotransmitters of the Autonomic Nervous System in Anesthetized Female Wistar Rats.
Authors: Cafarchio Eduardo Mazuco , Vale Bárbara , da Silva Daniel Santana , da Silva Luiz Augusto , Faccini Cristiane , Fonseca Fernando Affonso , Maifrino Laura Beatriz Mesiano , Sato Monica Akemi 
Published: June 2021

BackgroundThe effects of extracellular dehydration on the urinary bladder reactivity.AimTo investigate if different extracellular dehydration models affect urinary bladder reactivity to vasopressin and neurotransmitters of the autonomic nervous system in female Wistar rats.MethodsAdult female Wistar rats (N=6/group) one group the animals were in water deprivation for 24 hours and another group received a furosemide injection (50,0 mg/Kg S.C) and were maintained with sodium free diet. After all animals were anesthetized with 2% isoflurane in 100% O2 underwent to a cannulation of the femoral artery for mean arterial pressure and heart rate recordings. The urinary bladder was cannulated for intravesical pressure (IP) recordings. After baseline recording of the physiological parameters for 15 min, drugs (vasopressin 1 ng/mL, or acetylcholine 2 ug/mL, or noradrenaline 2 ug/mL) were administrated in situ (0.1 mL) on the urinary bladder and all the parameters were recorded for the control responses The AVP receptor subtypes were also labeled by immunofluorescence technique in the urinary bladder. Data are as mean±SE and were submitted to paired Student t‐test (p<0.001).ResultsThe water privation group responses in IP to vasopressin (39,5±1,0% vs. 110,1±1,9% control), acetylcholine (125,9±12,4% vs. 488,8±24,9% control), and noradrenaline (−17,5±1,0% vs. −67,6±1,6% control) were attenuated. Similarly the furosemide group the IP responses to vasopressin (42,8±2,8% vs. 110,1±1,9% control), acetylcholine (145,0±5,0% vs. 488,8±24,9% control), and noradrenaline (−28,8±1,0% vs. −67,6±1,6% control)were reduced. The immunofluorescence was showed a decrease in the amount of vasopressin receptors on the membrane of urinary bladder cells after dehydration in both models.ConclusionBoth models decreased the urinary bladder reactivity to vasopressin and to the neurotransmitters released by the autonomic nervous system innervation on the urinary bladder.Support or Funding InformationFinancial Support: FAPESP, CAPES and NEPAS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Iliocapsularis and Long Head of Triceps Brachii Innervation: Not Such “Textbook” Cases
Authors: Breckling Abbey , Jonees Michael W. , Ferrigno Christopher 
Published: June 2021

Anatomy instructors rely on accurate anatomical texts to facilitate instruction. While the understanding of anatomy continues to evolve, recent advancements are most reliably reflected in the vast amount of peer‐reviewed literature (PRL). Adjustments in anatomy textbooks (TBs), however, may take years to occur due to the publishing constraints such as illustrations and content vetting procedures. Consequently, TBs tend to lag behind the PRL with respect to new content. Subsequently, anatomy instruction may be dated despite the well‐intentioned instructor. Here we highlight two musculoskeletal‐focused discrepancies in anatomical PRL and TB literature: the presence of the Iliocapsularis (IC) and the innervation of the Long Head of Triceps Brachii (LHTB). To explore potential discrepancies, we used convenience sampling and audited 16 widely‐used TBs published within the past 10 years (3.1 ± 2.8 years) to determine the presence of IC and the innervation of the LHTB. We also analyzed PRL published within the past 18 years (5.4 ± 6.7 years) which focused on studies that used MRI or dissection to determine the presence of IC, and dissection only to explore the innervation of LHTB to the triceps. We conducted human dissection to verify the literature audit findings. To better evaluate the presence of IC, we dissected 22 anterior hips on preserved limbs in 11 cadavers and 5 unpreserved limbs in 3 cadavers. To better assess the innervation of the LHTB, we dissected the posterior shoulder and arm on 5 preserved limbs in 5 cadavers and 3 unpreserved limbs in 3 cadavers, with the aim of completing LHTB dissections on a minimum of 20 limbs. Out of 16 TBs reviewed, only 1 suggested the presence of IC and all reported the radial nerve as the innervation of LHTB (Table 1). Conversely, 4 PRL studies used dissection or MRI to assess the presence of IC and 3 studies used dissection to assess the innervation of LHTB by nerves other than the radial nerve (namely the axillary nerve) (Table 2). When pooling the individuals assessed in PRL, 100% were found to have an IC (n=271) and 72.2% were found to have a LHTB innervated by the axillary nerve. Our dissections of the anterior hips revealed that the IC was present in 100% of the 27 limbs. Our dissections of the posterior shoulder and arm revealed that the axillary nerve innervated the LHTB in 50% of the 8 bodies, including 2 of the 5 preserved limbs and 2 of the 3 unpreserved limbs. This study demonstrates that recently published TBs are not in alignment with the anatomical findings of our dissections or, more importantly, with the PRL. These findings suggest that anatomist instructors, as well as clinicians, should be familiar with recently published PRL and not rely solely on anatomical TBs.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification of Rapid Autonomic Adjustments Following Exercise at Onset of Isolated Post‐Exercise Muscle Metaboreflex Activation Using Continuous Wavelet Transform of Heart Rate Variability in Healthy Young Adults
Authors: Drew Rachel C. , Sánchez‐Hechavarría Miguel E. , Carrazana‐Escalona Ramón , Blaha Cheryl A. , Sinoway Lawrence I. 
Published: June 2021

Immediately following cessation of exercise, central command and muscle mechanoreflex inputs are removed but muscle metaboreflex input can remain in certain situations. Continuous wavelet transform allows analysis of heart rate variability (HRV) at times of rapid autonomic adjustments. However, it is unknown whether CWT can identify the rapid autonomic adjustments that occur immediately following cessation of exercise at the onset of isolated post‐exercise muscle metaboreflex activation. Therefore, we retrospectively applied CWT analysis to data previously collected from 14 healthy young adults (8 women/6 men; mean ± SD age 26 ± 2y) who performed one‐legged, isometric, calf exercise at 70% maximal voluntary contraction for 1.5 minutes, followed by circulatory occlusion via cuff inflation around the exercising limb that was maintained for 30 seconds to isolate muscle metaboreflex activation immediately post‐exercise. CWT analysis of R‐R intervals (electrocardiogram) included log‐transformed absolute and normalized low‐frequency (LF; 0.04–0.15Hz) and high‐frequency (HF; 0.15–0.4Hz) time‐frequency bands and the ratio of LF/HF for each of the six 5‐s time windows during the 30‐s muscle metaboreflex activation. Statistical analysis involved one‐way repeated measures analysis of variance with posthoc analysis. Absolute and normalized HF during 16–20s, 21–25s, and 26–30s following end‐exercise (4.73 ± 1.18, 4.90 ± 1.22, and 4.81 ± 1.10ms2, and 12.85 ± 10.37, 15.80 ± 12.04, and 14.99 ± 11.36 normalized units (nu), respectively) were higher than 1–5s following end‐exercise (3.6 ± 1.13ms2 and 5.01 ± 4.51nu, respectively; P < 0.05). Absolute LF was not different across time‐points (P < 0.05), but normalized LF during 16–20s, 21–25s, and 26–30s following end‐exercise (87.15 ± 10.37, 84.20 ± 12.04, and 85.01 ± 11.36nu) was lower than 1–5s and 6–10s following end‐exercise (94.99 ± 4.51 and 94.23 ± 4.44nu; P < 0.05). LF/HF during 11–15s, 16–20s, 21–25s, and 26–30s following end‐exercise (2.59 ± 0.80, 2.24 ± 0.97, 1.97 ± 1.00, and 1.99 ± 0.91) was lower than 1–5s following end‐exercise (3.32 ± 0.97; P < 0.05). In conclusion, CWT can identify the restoration of parasympathetic modulation of HRV and/or reduction in sympathetic modulation of HRV during the onset of isolated post‐exercise muscle metaboreflex activation in healthy young adults.Support or Funding InformationSupported by National Institutes of Health grants UL1 TR000127 and P01 HL096570.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypoxia‐Induced Ubiquitination Regulates 14‐3‐3η‐Gremlin‐1 Interactions in a Hypoxia Model of Pulmonary Hypertension.
Authors: Wade Brandy E. , Zhao Jingru , Ma Jing , Hart C. Michael , Sutliff Roy L. 
Published: June 2021

Pulmonary Hypertension (PH) is characterized by increased pulmonary artery pressure andresistance, right ventricle (RV) hypertrophy, RV failure and death. Increased vascular cell proliferation and vascularremodeling contribute to PH progression, though the mechanisms are incompletelydefined. The ubiquitin proteasome system (UPS)regulates cellular homeostasis through post‐translational modification oftarget proteins with ubiquitin moieties that direct protein degradation, protein‐proteininteractions, activity, or localization. Massspectrometry analysis of lungs from mice exposed to normoxia or hypoxia,revealed hypoxia‐induced changes in protein ubiquitination. Hypoxia caused a 2.4‐fold increase inubiquitination of 14‐3‐3eta (14‐3‐3η) at lysine (K)50 (p<0.05) with no change in 14‐3‐3η protein levels. Dysregulation ofthe 14‐3‐3 family of binding proteins is known to promote tumor cellproliferation and migration pathways. We hypothesized that 14‐3‐3η K50 ubiquitinationmay change protein activity since K49/50 is known to play an important role in14‐3‐3 function. K50 is also near the binding site for Gremlin‐1, a proteinthat promotes proliferation by inhibiting bonemorphogenetic protein (BMP)signaling. Immunoprecipitation of 14‐3‐3η from hypoxia‐exposed mouse lungdemonstrated that hypoxia reduced binding of 14‐3‐3η to Gremlin‐1. IncreasedGremlin‐1 to BMP2 binding was also observed in hypoxia‐exposed mouse lungs,suggesting that Gremlin‐1/BMP2 binding may contribute to disrupted BMPsignaling previously observed in hypoxia. Expression of a lysine to argininemutation at 14‐3‐3η K50 (K50R) whichprevents ubiquitination of K50 without altering the local polarity or shape inhuman pulmonary artery endothelial cells, promotes 14‐3‐3η/Gremlin‐1interaction in hypoxia. These findings demonstrate that K50 ubiquitination regulates14‐3‐3η function and its interaction with Gremlin‐1. We speculate thathypoxia‐induced increases in 14‐3‐3η K50 ubiquitination reduce Gremlin‐1 bindingwhich in turn binds BMP ligands to reduce BMP signaling and thereby promote vascularcell proliferation and PH pathogenesis.Support or Funding InformationMerit Review funding from the Department of Veterans Affairs, Office ofResearch and Development 1I01BX001910 (CMH), NIH Grant RO1HL102167 (CMH and RLS), NIH T32 HL076118 and 16POST30930007 (BEW). MS work was performed by the Emory Integrated Proteomics CoreThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Airway mechanoreceptors that control breathing
Authors: Chang Rui , Strochlic David , Nonomura Keiko , Patapoutian Ardem , Liberles Stephen 
Published: June 2021

The airways contain a myriad of sensory cells that mediate olfaction, control breathing, and protect the respiratory system from damage and disease. The vagus nerve is a major conduit between lung and brain required for normal respiration, and some vagal sensory neurons detect airway expansion that occurs with every breath. Mechanical inflation of the lungs and airways triggers a protective respiratory reflex termed the Hering‐Breuer inspiratory reflex, characterized by acute apnea. How vagal sensory neurons detect increases in airway volume was unknown at a molecular level. We initiated a molecular and genetic analysis of the sensory vagus nerve, identifying cell types that innervate the lung and powerfully control breathing. Moreover, we identified a critical role for the ion channel Piezo2 in airway mechanoreception. Optogenetic activation of vagal afferents containing Piezo2 causes apnea, trapping animals in a state of exhalation. Moreover, conditional deletion of Piezo2 from nodose ganglion‐derived sensory neurons eliminates sensory neuron responses to airway stretch as well as the classical Hering‐Breuer inspiratory reflex. These findings indicate a key role for Piezo2 as an airway stretch sensor critical for establishing efficient respiration at birth and maintaining respiratory homeostasis in adults. Understanding the sensory biology of respiratory control neurons in the vagus nerve may provide therapeutic targets for airway disease intervention.Support or Funding InformationHarvard‐MIT Joint Research Grants Program in Basic Neuroscience to S.D.L, R01DE022358 to A.P. and R01HL132255, and a Giovanni Armenise‐Harvard Foundation Grant to S.D.L. A.P. is an investigator of the Howard Hughes Medical Institute.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Disinhibition of Bötzinger Complex Abolishes Active Expiration Induced by Sustained Hypoxia in Rats
Authors: Zoccal Daniel B. , Amarante Marlusa K. , Flor Karine C. 
Published: June 2021

Exposure to sustained hypoxia, as experienced in high altitudes, elicits an increase in baseline ventilation that persists upon reoxygenation. We previously demonstrated that the increased baseline ventilation induced by short‐term sustained hypoxia (SH, 10% O2 for 24 hs) in rats is associated with the emergence of active expiration. However, the neural mechanisms underlying this respiratory pattern modification in SH rats remain unknown. In the present study, we hypothesized that alterations in the Bötzinger complex (BötC) activity, an important inhibitory region of the respiratory network, play a role in the generation of active expiration in SH rats under resting conditions. Using the decerebrated, arterially perfused in situ preparation of rats previously exposed to normoxia (control) or SH, we pharmacologically manipulated the activity of BötC as well as evaluated the activity of expiratory neurons in this region while recorded the activity of phrenic (PN), central vagus (cVN) and abdominal nerves (AbN). The in situ preparations of SH rats (n=8) exhibited augmented baseline abdominal activity, with the emergence of additional bursts during late phase of expiration, which were not seen in controls (n=8, P<0.05). Disinhibition of the BötC, with bilateral microinjections of strychnine (glycine receptor antagonist, 10 μM, 30–40 nl/side), eliminated the active expiratory bursts in the AbN activity and restored the eupneic‐like respiratory pattern in SH rat preparations (n=8, P<0.05). Bilateral microinjections of strychnine in the BötC of control preparations (n=7) caused small reductions in all nerve amplitudes (P<0.05), without disrupting the 3‐phase respiratory pattern. We also found that the BötC post‐inspiratory (post‐I) neurons in SH preparations (n=2) exhibited an earlier shut down during the expiratory phase compared control group (n=3, P<0.05), which was coincident with the emergence of AbN expiratory bursts. In contrast, the BötC augmenting‐expiratory neurons (aug‐E) of SH preparations (n=3) exhibited an anticipated onset in comparison to the aug‐E activity of control preparations (n=2, P<0.05). Altogether, our data indicate that the neurons of the BötC exert an inhibitory control on the mechanisms underpinning the pattern of active expiration in SH rats. Based on our neuronal recordings, we speculate that this inhibitory control of the BötC might be driven by the post‐I population.Support or Funding InformationFAPESP (2013/17.251‐6; 2015/23568‐8)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ventilatory CO2/H+ Chemoreflex During Chronic Hypercapnia in Healthy Goats
Authors: Burgraff Nicholas , Buchholz Kirstyn , Neumueller Suzanne , Hodges Matthew , Pan Lawrence , Langer Thomas , Forster Hubert 
Published: June 2021

Respiratory disease patients that hypoventilate and develop chronic hypercapnia often show poorer prognoses, decreased quality of life, and higher mortality rates compared to similar disease patients that maintain pulmonary ventilation and arterial CO2. Herein, we sought to determine the effect of chronic hypercapnia on the temporal pattern of the acute ventilatory and diaphragmatic EMG responses to increasing PaCO2 by exposing goats to either room air or an elevated inspired CO2 (InCO2) to 6% for up to 15 days. On several days, InCO2 was further increased to 7 and then 8% to assess ventilatory and diaphragmatic EMG responses. CO‐2 sensitivity (ΔVI‐/ΔPaCO2) progressively declined during the first 5 days of hypercapnia, reaching a nadir of 31% below control on day 5 of hypercapnia. Similar declines during the first 5 days of chronic hypercapnia were observed in the tidal volume (VT), breathing frequency (f), integrated diaphragmatic EMG (Dia EMG), ventilatory drive (VT/TI), and peak inspiratory flow responses as a function of PaCO2 during acute elevations to 7 and 8% InCO2 ranging from 39–62% below control by day 5. Following the initial decline in responses, there was a recovery of the VI, VT, f, Dia EMG, VT/TI, and peak inspiratory flow responses to control levels between days 8–15. The V‐I−/H+ relationship during acute increases to 8% InCO2 remained unchanged over the 15 days. However, VI/H+ at 6% InCO2 was ~200% above control from 2–15 days of chronic hypercapnia, suggesting a disconnect between the chronic VI/H+ relationship at 6% InCO2 and the VI−/H+ relationship during acute elevations to 8% InCO−2. The relationship between inspiratory flow and diaphragm EMG activity decreased to 69% of control by day 2 of hypercapnia, followed by a sustained increase to 149–248% above control thereafter, indicative of further respiratory muscle recruitment or increased dilatory effects on the airways. In summary, we have established a model to determine the effects of chronic hypercapnia on the temporal pattern of ventilatory CO−2/H+ sensitivity. Results from this study may provide insight into the role of hypercapnia in the progression of respiratory disease adaptation.Support or Funding Information‐Department of Veteran Affairs; NIH HL007852This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute and Chronic Respiratory Effects from Repeated Audiogenic Seizures in SSKcnj16−/− Rats
Authors: Manis Anna D. , Mouradian Gary C. , Alvarez‐Argote Santiago , Staruschenko Alexander , Palygin Oleg , Hodges Matthew R. 
Published: June 2021

Kir5.1 is a member of an inwardly rectifying potassium (Kir) channel family highly expressed in the kidney and brain. Mutations in ion channel genes can alter neuronal excitability, and mutations in related Kir genes have been linked to seizure disorders in humans. We previously established that a knockout rat model of Kcnj16 (gene encoding Kir5.1) on a Dahl salt‐sensitive background (SSKcnj16−/−) exhibits a severe cardiovascular phenotype (Palygin et al., JCI Insight, 2017) as well as an audiogenic reflex epilepsy phenotype. SSKcnj16−/− rats, but not control SS rats, experience tonic‐clonic seizures when exposed to a 10 kHz tone (86 dB for 2 min). Although seizures are typically considered benign events, patients with uncontrolled epilepsy are 27 times more likely die of Sudden Unexplained Death in Epilepsy (SUDEP) compared to those without epilepsy, presumably due to cardiorespiratory failure associated with repeated seizures. Here, we tested the hypothesis that repeated audiogenic seizures would acutely and chronically alter breathing in SSKcnj16−/− but not control SS rats. SSKcnj16−/− and control rats were exposed to the acoustic stimulus once/day for 10 days while using plethysmography to measure breathing before, during, and after exposure. SSKcnj16−/− rats show a marked increase in tidal volume (1.4 ± 0.1 to 3.2 ± 1.2 mL/100g) after acoustic stimulation which becomes more pronounced after exposure to 10 acoustic stimuli (1.7 ± 0.1 to 4.2 ± 1.1 mL/100g). Minute ventilation and drive to breathe show similar increases with successive acoustic exposures. SS control rats do not show changes in tidal volume or minute ventilation over the 10 days. In addition, we see a substantial increase in resting VO2 between day 1 (7.4 ± 0.4 mL/min/100g) and day 10 (11.8 ± 0.6 mL/min/100g) of acoustic stimulation in SSKcnj16−/−/− rats but not controls. During the 10 days of stimulation, we observed spontaneous mortality in 33% of SSKcnj16−/− rats (N = 7 of 21 total) within hours of a seizure, while 100% (N=12) of control SS rats survived. We found no difference among male and female SSKcnj16−/− rats, where both sexes had a similar audiogenic seizure response and reduced survival. Further studies into the mechanisms behind seizure‐induced death in SSKcnj16−/− rats could have central relevance to the pathophysiology of SUDEP, which remains poorly understood.Support or Funding InformationNIH HL122358This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.