bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of kidney on sodium balance in AngiotensinII‐induced hypertension.
Authors: Ferreira‐Figueiredo Claudia S.R. , Oliveira‐Souza Maria 
Published: June 2021

AimInvestigate the renal function and modulation of epithelial transporters of rats with angiotensin‐induced hypertension.MethodsNormal 8‐week‐old male Wistar rats were divided in two groups: control (sham) or treated with 200 ng/kg/min of angiotensin II (ANG II) for 28 days, using osmotic minipumps. Blood pressure (BP) was monitored weekly by tail cuff plethysmography. Renal plasmatic flow (RPF) and glomerular filtration rate (GFR) were determined by para‐aminohippurate sodium and inulin clearance, respectively. The excretion of ions was analyzed and proteic expression of renal transporters or ANG II receptors will be analyzed by Western Blot technique.Results and DiscussionOur preliminary results animals showed that the dose of ANG II used is sufficient to induce hypertension [110 ± 1,6 (sham) n = 4 versus 158 ± 1,7 (ANG II) mmHg n = 4 *p<0,001]. Urinary Na+ and K+ were reduced in hypertensive rats. RPF and GFR were also reduced [RPF = 13,29 ± 0,8 (sham) n = 14 versus 6,48 ± 0,44 (ANG II) ml/min/kg n = 14 *p<0,001] and [GFR = 8,4 ± 0,52 (sham) n=14 versus 4,73 ± 0,52 (ANG II) ml/min/Kg n = 14 *p<0,001], suggesting changes in renal hemodynamics and tubular function. However, epithelial transporters will be analyzed in the renal cortex and medulla. Financial Support: CNPq and FAPESP
The Ca2+‐activated Cl‐ channel TMEM16A represents the effector pathway for purinergic receptor‐mediated secretion in liver epithelium.
Authors: Dutta Amal Kumar , Khimji Al‐Karim , Dougherty Michael , Kresge Charles , Woo Kangmee , Esser Victoria , Alpini Gianfranco , Rockey Don 
Published: June 2021

In the liver, Cl− channels in the apical membrane of biliary epithelial cells (BECs) provide the driving force for biliary secretion. Extracellular nucleotides are important agonists for Ca2+‐activated Cl‐ channel activation. The molecular identity of the Ca2+‐activated Cl‐ channel is unknown.Aimto determine if TMEM16A represents the Ca2+‐activated Cl− channel in BECs.MethodsStudies were performed in human, mouse, and rat BECs. Membrane Cl− currents were measured by whole‐cell patch clamp and transepithelial secretion (Isc) by Ussing chamber.ResultsTMEM16A mRNA was detected by RT‐PCR in all BEC models. In polarized BEC monolayers, addition of ATP to the apical chamber increased Isc. Pre‐incubation with IL‐4 increased TMEM16A expression and was associated with an increase in Isc. The ATP‐stimulated Isc was completely inhibited by the Cl− channel blockers NPPB and niflumic acid, but insensitive to CFTR‐inh172. In single cells, exposure to ATP rapidly increased [Ca2+]i and activated whole‐cell Cl− currents with a reversal potential of 0 mV and outward rectification. Transfection with TMEM16A siRNA significantly decreased TMEM16A expression and inhibited the ATP‐stimulated whole‐cell currents.ConclusionThese results demonstrate that TMEM16A is functionally present in BECs and contributes to Ca2+‐activated Cl− secretion in response to extracellular nucleotides. These studies represent the first molecular identification of an alternate, non‐CFTR, Cl− channel in BECs.
Wound repair in type I alveolar epithelial cells involves lysosome secretion followed by initiation of actin repolymerization
Authors: Godin Lindsay Marie , Vergen Jorge , Prakash Y.S. , Hubmayr Rolf 
Published: June 2021

Stress failure of alveolar epithelial cells is a common feature of ventilator‐injured lungs. While some injured cells undergo necrosis, others repair their plasma membrane (PM) wounds through non‐secretory exocytosis of intracellular vesicles (e.g. lysosomes) to and cytoskeleton remodeling at and around the wound. We measured the timing of lysosomal trafficking and F‐actin reorganization following micropuncture injury in primary type I alveolar epithelial cells (ATI).ATI were isolated from female rats and loaded with Calcein AM, N‐rhodamine phosphatidylethanolamine (lysosome membrane label) or transfected with LifeAct (GFP tagged actin label). Changes in fluorescence intensity were indicators of time to wound repair (cessation of calcein fluorescence decay following injury), lysosomal trafficking to the wound site, and actin remodeling.ATI repaired wounds within 27.9±3.9s. Recruitment of lysosomes to the wound site was detected at 2.9±1.5s following injury and preceded actin polymerization by 23.7±5.4s. Failure to repair PM wounds was associated with a weak or absent actin polymerization response.We conclude that local actin polymerization is a critical step in PM wound repair and postulate that adhesive interactions between PM lipids and the remodeled actin cytoskeleton serve as a driving force for wound closure by promoting lateral PM lipid bilayer flow.Support: HL63178
Impact of untranslated regions (UTRs) on differential translation among SftpA1 and SftpA2 gene variants
Authors: Silveyra Patricia , Wang Guirong , Floros Joanna 
Published: June 2021

Surfactant protein A (SP‐A) plays an important role in host defense and surfactant‐related functions. In humans, SP‐A is encoded by two genes (SftpA1, SftpA2). Structural and functional differences between SftpA1 (SP‐A1) and SftpA2 (SP‐A2) products have been observed; as well as splice and sequence variation, respectively, at the 5′UTR and 3′UTR. Here, we studied the role of SP‐A 5′UTR and 3′UTR variants, and polyA on translation. We generated constructs (n=14) with the luciferase reporter gene flanked by SPA 5′UTR (SP‐A1: AD′; SP‐A2: ABD, ABD′) and/or 3′UTR (SP‐A1: 6A2, 6A4; SP‐A2: 1A0, 1A3). mRNA was obtained in vitro and polyA was added or omitted. NCI‐H441 cells were transfected and luciferase activity was measured.Results1) in the absence of 3′UTR, the SP‐A 5′UTRs exhibit an additive effect with polyA and stimulate translation with different efficiencies (ABD=ABD′>AD′> no 5′UTR); 2) in the absence of 5′UTR, 3′UTR increased translation; with no differences among variants; 3) the combination of SP‐A 5′UTR and 3′UTR showed an additive effect on translation. In this context, the SP‐A1 6A4 3′UTR variant showed higher translation than 6A2, whereas no differences were observed between SP‐A2 3′UTRs (1A0, 1A3).ConclusionThe 5′UTR, 3′UTR, and polyA contribute to the differential translation of SP‐A1 and SP‐A2. However, the SP‐A1 3′UTR appears to regulate variant‐specific translation. (Supported: NIH HL‐34788)
Cardiovascular responses to standing and walking in earth and simulated moon and mars gravities
Authors: Evans Joyce M , Kilfoil Peter J , Wang Siqi , Mohney Lindsay , Knapp Charles F 
Published: June 2021

IntroductionHuman cardiovascular responses to standing and walking in simulated reduced gravity were measured using a treadmill enclosed in a lower‐body positive pressure (LBPP) chamber (AlterG device).MethodsHeart rate, HR, continuous blood pressure, BP, (Portapres), segmental fluid shift (THRIM), diastolic function and stroke volume (Biosounds) were recorded on 7 subjects (4 males, 3 females) at supine and while standing and walking under 100% (earth), 40% (mars), and 20% (moon) body weights (BW).ResultsSubjects standing at 20% and 40% BW had reduced HR (p<0.01), increased systolic BP (p<0.05) and increased thoracic impedance (p<0.001) compared to standing. Reduced BW was associated with increased upper and lower leg impedance (loss of fluid volume, p<0.05). Stroke volume was greatest while supine, at 20%, 40% BW and walking compared to standing (p<0.01). Mitral E to A ratio was reduced for 20%, 40%, and 100% BW compared to supine (p<0.01). The number of blood pressure ramps and baroreflex sequences decreased as body weight was reduced.ConclusionFluid redistribution in the body and short‐term cardiovascular changes induced by Alter‐G unloading are compatible with those resulting from exposure to microgravity. Supported by KY NASA EPSCoR 52611.
The effect of simulated 1/6th and 1/3rd gravity on gastrocnemius muscle mass and fractional protein synthesis rates in mice
Authors: Wiggs Michael Parker , Swift Joshua M , Lima Florence , Greene Elizabeth S , Bloomfield Susan A , Fluckey James D 
Published: June 2021

During periods of disuse or unloading (0G), there is a substantial decline in mass and function of skeletal muscle. However the effects of partial weight bearing, similar to Lunar (G/6) or Martian (G/3) gravitational fields, have yet to be determined. We used a partial G mouse model to assess graded reductions in weight bearing on skeletal muscle. We hypothesized that mice exposed to 21 days of G/6 and G/3 would experience significant reductions of gastrocnemius (gastroc) mass compared ambulatory control animals (1G), but that the magnitude of these changes would be less than in 0G mice. Further, decrements of fractional protein synthesis rates (FSR) would be consistent with reductions of muscle mass. Female BALB/cByJ (4 month old; n=43) mice were randomly assigned to fill four groups (1G, 0G, G/6 or G/3). After a 21‐day suspension period gastroc muscles were excised and weighed, and cumulative FSR was assessed using deuterium oxide. Total body mass was similar among groups (p>0.05). However, wet weight of gastroc was lower in G/6 and G/3 compared to 1G (p<0.05), and even lower in HU (p<0.05 vs 1G, G/6 and G/3). FSR was not different among 1G, G/6 and G/3, but was lower in 0G animals (p <0.05). This study shows that muscle mass is related to applied load but partial loading is able to maintain FSR.Funded by National Space Biomedical Research Institute via NASA Cooperative Agreement NCC 9‐58
Treatment with swimming and treadmill exercises reduced neuropathic pain on chronic constriction injury of sciatic nerve of rats
Authors: Li Yung Tsung , Li Zong Ying , Hsueh Meng I , Hung Hui Chun , Ou Hsiu Chung , Chen Yu Wen 
Published: June 2021

BACKGROUNDTreatment of neuropathic pain is still a challenge. Pharmacotherapies provide an effective efficacy for treatment of neuropathic pain, but drugs produce some side effects. Whether exercise training without drug treatment could provide beneficial effects on neuropathic pain.MATERIALS AND METHODSChronic constriction injury (CCI) of the sciatic nerve in male SD rats produces behavioral hypersensitivity and is an accepted model of neuropathic pain. All rats were divided into 6 groups: sham, sham with swimming/treadmill exercise, CCI, CCI with swimming/treadmill exercise. We compared behavior responses and body weight in sham operated and CCI rats with or without exercise training. Thermal hyperalgesia and tactile allodynia was assessed by Plantar test and von Frey filament test.RESULTSOur results showed that treatment with swimming and treadmill exercises attenuated thermal hyperalgesia and mechanical allodynia significantly in the CCI rat. The change trend of body weight indicated no significant differences between each group but not the sham group.CONCLUSIONOur preliminary results support both swimming and treadmill exercises training attenuated neuropathic pain in the rat. This study was supported partially by a grant from the China Medical University (CMU98‐S‐35) of Taiwan.
Early exercise training attenuates left ventricular dysfunction, myocardial infarction area and molecular abnormalities in diabetic rats
Authors: Rodrigues Bruno , Jorge Luciana , Malfitano Christiane , Medeiros Alessandra , Rosa Kaleizu Teodoro , Alba‐Loureiro Tatiana , Candido Georgia Orsi , Curi Rui , Lacchini Silvia , Brum Patricia Chakur , De Angelis Kátia , Irigoyen Maria Cláudia 
Published: June 2021

In this study we evaluated the effects of early exercise training (ET) on mortality rate, myocardial infarction (MI) area and VEGF gene levels, as well as on left ventricular (LV) function and calcium handling abnormalities in diabetic rats after MI. Male Wistar rats were divided in sedentary (S) and exercise training (ET) groups: control (C), MI+S (SI), MI+ET (TI), diabetes+MI+S (SDI) and diabetes+MI+ET (TDI). After 20 weeks of ET, MI size although similar at the beginning (~40±3%), was reduced at the end of the protocol in trained groups. MI size reduction was associated with increased mRNA VEGF levels in trained animals. Trained rats displayed higher cardiac output and ejection fraction (TI: 59±4 and TDI: 58±4% vs SI: 40±1 and SDI: 54±1%) when compared to sedentary ones. This improvement on LV function in trained animals was associated with increased expressions of SERCA2 (25%) and phospholamban phosphorilated at serine 16 (34%). In addition, survival rate was improved after ET period (TI: 87 vs SI: 41% and TDI: 75 vs SDI: 30%). These results showed that early ET intervention induced MI area reduction, LV function and survival improvement in trained animals. Moreover, the improvement of mRNA VEGF levels and Ca2+ handling proteins gives support to consider ET as a coadjuvant therapy able to induce additional changes at myocardium molecular levels in diabetic subjects after an ischemic event.CNPq
Endurance exercise protects cardiac tissue from doxorubicin‐induced proteolysis and apoptosis
Authors: Kavazis Andreas N , Smuder Ashley J , Min Kisuk , Tümer Nihal , Powers Scott K 
Published: June 2021

Doxorubicin (DOX) is an antitumor agent used in cancer treatment. Unfortunately, the clinical use of this highly effective drug is limited due to cardiotoxicity. We hypothesized that endurance exercise would result in upregulation of cardiac antioxidant enzymes and heat shock protein 72 which would protect against DOX‐induced proteolysis and apoptosis. Adult male rats were divided into sedentary or exercise groups followed by placebo or DOX treatment. Our results indicate that DOX promotes disturbances in cardiac muscle redox balance (i.e. increased levels of 4‐hydroxynonenal and protein carbonyls). Furthermore, the activities of calpain and caspase‐3 were significantly increased in cardiac tissue of sedentary animals treated with DOX. Importantly, exercise prior to DOX treatment blunted the increased cardiac protein oxidation and protease activation. Furthermore, exercise reduced the number of apoptotic nuclei in the heart following DOX treatment. These results suggest that DOX‐induced cardiotoxicity may be attributed to disturbances in cardiac muscle redox balance, increased proteolytic activity, and apoptosis. Importantly, data from these experiments suggest that endurance exercise may act to preserve these detrimental side effects of DOX treatment in cardiac tissue.Supported by AHA (to ANK), NIH R01 HL087839 (to SKP) and Medical Research Service, Dept. of Veterans Affairs (to NT)
Responses of nucleus tractus solitarius neurons to vanilloid, purinergic and CCK receptor activation
Authors: Browning Kirsteen N , Travagli R. Alberto 
Published: June 2021

Recent reports indicate that cardiovascular sensory inputs to neurons in the nucleus tractus solitarius (NTS) can be distinguished based on their response to vanilloid‐ or to purinergic‐ agonists, active only on C‐ or A‐δ fibers respectively.The NTS subnucleus centralis (cNTS) receives vagal afferent inputs from subdiaphragmatic viscera and is involved in vago‐vagal circuits controlling gastrointestinal (GI) motility. We have shown that CCK‐8s increases glutamate release from vagal afferent fibers onto cNTS neurons. Since CCK‐8s is thought to exert its GI‐related effects via activation of C‐fibers only, we aimed to test whether vanilloid and CCK‐8s sensitive inputs to cNTS neurons were distinguishable from those responsive to purinergic agonists. Spontaneous EPSCs were recorded from cNTS neurons in response to perfusion with capsaicin (CAP), α‐β‐met‐ATP (ATP) and/or CCK‐8s.ATP, CAP or CCK‐8s increased sEPSC frequency in 37, 75 and 43% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK‐8s and ATP, to CCK‐8s and CAP, or to ATP and CAP while 32% of the neurons were responsive to all three agonists. Interestingly, all neurons responding to ATP or CCK‐8s were also responsive to CAP.Thus, unlike cardiovascular sensory inputs, C‐ and A‐δ inputs to cNTS neurons do not appear to have selective responses to either ATP or CAP.Supported by DK 55530
Age‐related changes in autonomic control during sleep: symbolic and complexity analyses of heart rate variability
Authors: Tobaldini Eleonora , Viola Antoine , Chellappa Sara , Porta Alberto , Casali Karina R , Montano Nicola 
Published: June 2021

Scanty data are available on the differences in neural control of circulation during sleep between young (Y) and older (O) subjects. The aim of our study was to assess the age‐related changes of heart rate variability during sleep using symbolic analysis (SA) and entropy indexes, Shannon entropy (SE) and Conditional Entropy (CE). A polysomnography was performed in 12 Y and 12 O healthy volunteers; time series of RR intervals were constructed for each sleep stage (Wake, W; slow wave sleep, SWS; and REM) and analyzed using SA, SE and CE.SA is based on the conversion of time series into symbols, the construction of patterns and the identification of four families: 0V (no variation), marker of sympathetic modulation, 1V, 2LV and 2UV (two unlike variations), marker of parasympathetic modulation. SE and CE measure the amount of information carried by the new sample when the previous are known. A decrease of entropy indexes is marker of aging and disease.In the O, REM was characterized by a decrease of SE, CE and 2UV% and an increase of 0V%, with respect to SWS and W. Compared to Y, the O showed in all stages a reduction of SE, CE and 2UV% and an increase of 0V%, and these differences were more evident during REM sleep.In conclusion, REM is characterized by a decrease of complexity and a predominance of sympathetic modulation in older subjects and it may represent a state of increased risk for cardiovascular events during aging.
Effects of exercise on miRNA expression levels in human peripheral blood mononuclear cells (PBMCs)
Authors: Radom‐Aizik Shlomit , Zaldivar Frank , Oliver Stacy , Galassetti Pietro , Cooper Dan M 
Published: June 2021

Brief exercise results in substantial changes in gene expression of circulating PBMCs. Moreover, many key gene pathways influenced by exercise are related to inflammation. We hypothesized that microRNAs (small 21–23 nucleotide non‐coding RNAs) would also be changed by exercise and act to prevent a predominantly pro‐inflammatory PBMC response that could be dangerous. 12 healthy men (19–30 y.o.) performed 20 min of cycle ergometry (~75% peak VO2). PBMCs were isolated before and after the exercise. Using the Agilent Human miRNA Microarray (V2), we found that exercise altered 94 miRNAs (FDR=0.2; 61 downregulated). Many of the miRNAs altered by exercise are known to play mechanistic roles in other inflammatory processes [e.g., miR‐125b(↓) and miR‐146a(↓) which are downregulated by proinflammatory factors LPS and TNF‐α, respectively). We also found exercise effects on miRNAs associated with B‐cell development, e.g., miR‐181a(↑), ‐150(↓), and ‐17(↓). Further, we compared the miRNA changes in PBMCs with the 38 miRNAs in neutrophils that we previously found to have been altered by exercise. 18 miRNAs were affected in both PBMCs and neutrophils, but only 12 changed in the same direction. In conclusion, brief heavy exercise changes miRNA profiles in PBMCs many of which are related to inflammatory processes. The pattern of change suggests that exercise differentially influences miRNAs in leukocyte subtypes.Grants: Supported by NIH grants P01‐HD048721 and RO1‐HL080947
Maternal Exercise Dose Response Effect on Fetal Heart Rate and Variability
Authors: May Linda E , Glaros Alan G , Gustafson Kathleen M , Suminski Richard R 
Published: June 2021

We did a retrospective analysis to determine if there was a dose response relationship between maternal exercise and fetal heart rate (HR) and heart rate variability (HRV). We used hierarchal linear regression of 36 wk data from MCG recordings and activity questionnaires. Associations between maternal kilocalories per min (kcal/min) and total kcal expended (Tkcal) during exercise and fetal HR and HRV (ie. SDNN, RMSSD, VLF, LF, HF) were examined. We controlled for maternal resting HR, maternal weight, maternal kcal while sedentary, and fetal activity state. In univariate analysis, SDNN, VLF, and LF were positively correlated with Tkcal (p<0.05) and fetal HR was negatively correlated. SDNN and HF were positively correlated with kcal/min (p<0.05). After controlling for confounders, significant associations were found with Tkcal and SDNN (t=2.7) and between kcal/min and fetal HR (t = −2.3), RMSSD (t= 2.2), and HF (t=2.2). Maternal exercise variables explained significant portions of the variance in fetal measures: HR (17.8%), RMSSD (15.5%), SDNN (20.4%), and HF (15.7%). Maternal exercise intensity and energy expenditure has a dose response effect on the fetal heart consistent with the development origins hypothesis. These findings will guide future studies using exercise as an intervention for improving maternal and fetal outcomes in pregnancies complicated by gestational diabetes, obesity and hypertension.Research supported by: KCUMB and Hoglund Brain Imaging Center fundsGrant Funding Source: KCUMB
Eukaryon: An undergraduate peer‐reviewed and managed life sciences scholarship journal
Authors: Fiske Michael , DebBurman Shubhik , Smith Pliny , Davis Shaun 
Published: June 2021

Undergraduate research and inquiry‐based pedagogy are increasingly crucial components to college education in the U.S. Providing undergraduates the opportunity to publish their scholarship is a tool to increase scientific literacy and motivation for scientific careers. Spurred by an NSF grant in 2004, the Lake Forest College Biology Department developed a peer‐reviewed undergraduate research journal of life science scholarship entitled Eukaryon (http://www.lakeforest.edu/eukaryon). In each annual issue, Eukaryon publishes scholarship in the life sciences that students produced within undergraduate classrooms and faculty labs. We detail three aspects of the journal's development: 1) how it is governed, published, and financed by undergraduates; 2) how it establishes content and format; and 3) specific strategies that maintain selectivity, encourage inquiry‐based curriculum, and support a community of student scholars. Next, we discuss a survey‐based assessment of our journal's impact on curriculum and student community. We found that Eukaryon contributes significantly to the preparedness for future careers of its board members. Finally, we report an analysis of our online readership using data from Google Analytics. Future goals include strengthening community familiarity with Eukaryon and improving communication with faculty on submission and review progress.(Supported by NSF‐CCLI)
Calcified Integumentary Structures in Anurans
Authors: Delorme Stephanie , Vickaryous Matthew Kenneth 
Published: June 2021

Although often overlooked, the integument of many vertebrates is reinforced by skeletal elements. In anurans these calcified structures include osteoderms, bone‐rich elements, and the lamina calcarea, a calcified, acellular layer that lacks collagen. We investigated the histology of anuran integument with a special focus on taxa developing skeletal elements. When present, the lamina calcarea forms a thin but discrete horizon at the interface between the superficial and deep dermis. This layer is rich in glycosaminoglycans (GAG) and is structurally unlike bone and cartilage. In contrast, anuran osteoderms are composed of cellular bone with limited GAG. A partial ontogenetic series of the tree frog Phyllomedusa bicolor provides the first details of anuran osteoderms development. In P. bicolor osteoderm development begins as a cluster of small calcified centres localized over the head. With continued body growth, osteoderms become larger in size and become distributed across the dorsal and ventral surfaces of the body, and across the limbs. The leaf litter frog Brachytarsophyrys cariensis is unusual in developing both osteoderms (on the dorsal body surface) and a lamina calcarea (on the ventral body surface). Our data shows that anuran integument has the ability to form skeletal elements and suggests that these elements arose in multiple anuran lineages.Grant Funding Source: NSERC