bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium Induces Cilia Expression in Renal Intercalated Cells
Authors: Nair Anil V. , Franken Gijs , Paunescu Teodor , Capen Diane , Brown Dennis 
Published: June 2021

Lithium remains a first line drug for treatment of bipolar disorder (BD). It has demonstrated efficiency for the prevention of recurrence of mood episodes, and also as an enhancement strategy in major depressive disorder. Current research and a growing number of publications predict a wider role for Li in the coming years for various neurological disorders. One major limitation of Li treatment is the short‐ and long‐term adverse effects it has on the kidney in a subpopulation of its recipients. Up to 40% of Li receiving patients report various degrees of acute increase in urine production ‐ Nephrogenic Diabetes Insipidus (NDI). Long‐term Li treatment has a more severe side effect known as Chronic Kidney Disease (CKD), characterized by reduced glomerular filtration rate, interstitial nephritis, renal fibrosis, microcyst formation, ultimately leading to end‐stage renal disease. Renal cyst formation has also been implicated as a ciliopathy in polycystic kidney disease. Here, we studied the effect of Li on cilia in a mouse model treated for 3 months. Using immuno‐fluorescence, we imaged cilia in 16 μm thick sections of paraformaldehyde‐fixed mouse kidney. Cilia were labeled using an antibody against acetylated alpha‐tubulin. The 3D confocal images were deconvolved using Volocity software, and ciliary length from control and Li‐treated animals was measured in different tubule segments. In the different tubule segments, the mean length of cilia was different, but was not affected by Li except in the cortical collecting duct, where Li treatment significantly increased ciliary length from 6.6±0.4 μm to 7.7±0.3 μm. Collecting ducts are composed of two major cell types, intercalated (ICs) and principal cells (PCs), which were identified by the expression of cell type‐specific markers, the vacuolar proton‐pumping ATPase and aquaporin‐2, respectively. Among epithelial cells in the kidney, ICs are the only cell type that was never shown to express primary cilia. Remarkably, we found that Li treatment induces cilia expression in ICs. Li treatment is known to increase the ratio of ICs to PCs. Whether bona fide ICs are growing cilia de novo in response to Li treatment, or we are detecting PCs that have converted into ICs but still have a residual cilium that is not completely reabsorbed, remains to be elucidated.Support or Funding InformationNational Institutes of Health Grant DK096586 (D. Brown)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence Of “Priming” Exercise On Pulmonary Oxygen Uptake Kinetics During Heavy‐Intensity Cycle Exercise From An Elevated Baseline In Type 2 Diabetes.
Authors: Gildea Norita , Rocha Joel , Green Simon , O'Shea Donal , Egaña Mikel 
Published: June 2021

In healthy individuals phase II oxygen uptake (V̇ O2) kinetics (τ V̇ O2p) is slower when heavy‐intensity exercise is initiated from a moderate‐intensity exercise baseline (work‐to‐work) than unloaded cycling; but τ V̇ O2p is not enhanced when work‐to‐work exercise is preceded by a prior bout of heavy‐intensity priming exercise (PE). This negates an insufficient muscle O2 availability as the primary culprit in healthy individuals.PurposeGiven that type 2 diabetes (T2D) induces a lengthened τ V̇ O2p during unprimed submaximal exercise compared with healthy controls, which is attributed, at least in part, to limitations in O2 supply, the purpose of the study was to test the hypothesis that heavy‐intensity PE would subsequently accelerate τ V̇ O2p in T2D.MethodsSeven middle‐aged individuals with T2D (46 ± 8 yr) and 7 controls (ND) (41 ± 10 yr) performed four bouts of constant‐load, heavy‐intensity exercise each commencing from a baseline of moderate‐intensity exercise. Two of these work‐to‐work bouts were completed without PE and two bouts were undertaken preceded by PE. V̇O2 kinetics was calculated from continuously measured breath‐by‐breath V̇O2 data, whilst the rate of muscle deoxygenation (i.e., deoxygenated haemoglobin and myoglobin, HHb+Mb) was continuously measured by near‐infrared spectroscopy at the vastus lateralis muscle. Diabetes and priming comparisons were made using two‐way ANOVA with repeated measures.ResultsThe amplitude of the V̇O2 slow component was reduced (P < 0.05) in both groups following PE (T2D: from 0.13 ± 0.15 to 0.08 ± 0.10 l/min; ND: from 0.20 ± 0.18 to 0.12 ± 0.11 l/min). In addition, PE tended to reduce τ V̇ O2p during work‐to‐work cycling transitions in T2D (from 54 ± 14 to 42 ± 17 s) but not in ND (42 ± 11 vs. 41 ± 11 s), bringing the τ V̇ O2p in T2D on a par with their ND counterparts, in the absence of significant changes in the dynamic response of (HHb+Mb). It is likely inter‐individual variability in response precluded the attainment of statistical significance.ConclusionIn middle‐aged individuals with T2D, the enhanced V̇ O2 kinetics response was likely consequent to a priming‐induced increase in muscle blood flow and/or improved muscle perfusion to metabolic rate.Support or Funding InformationThis publication has emanated from research conducted with the financial support of the Health Research Board of Ireland (Grant No HRA_POR/2073/274)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inorganic nitrate supplementation improves exercise tolerance and calf vascular function in patients with peripheral artery disease
Authors: Bock Joshua , Treichler David , Ueda Kenichi , Hughes William , Casey Darren 
Published: June 2021

Peripheral artery disease (PAD) is characterized by widespread atherosclerotic development and endothelial dysfunction in the vasculature. This pathological process leads to hypoperfusion of local tissues, increases dependence on anaerobic metabolism, and induces the hallmark symptom of PAD; ischemic claudication. Additionally, PAD is associated with reductions in the bioavailability of nitric oxide (NO), a known regulator of vasodilator function. Together, ischemic claudication and reduced NO bioavailability attenuate exercise tolerance in PAD patients. Inorganic nitrate (NO3−) supplementation boosts NO bioavailability independent of NO‐synthase enzymes, subsequently improving vasodilator function and enhancing skeletal muscle oxygenation. Thus, inorganic NO3− supplementation may improve exercise tolerance in PAD patients. We therefore investigated if eight weeks of sodium NO3− (NaNO3) supplementation would improve exercise tolerance (six‐minute walk test, 6MWT) as well as calf blood flow or vasodilation in response to reactive hyperemia (strain gauge plethysmography) in patients with PAD. Twenty‐one patients diagnosed with moderate‐to‐severe PAD (ankle‐brachial index 0.80±0.07) were randomly assigned to NaNO3 (1g/day; n=13) or placebo (microcrystalline cellulose; n=8) supplementation groups. Eight weeks of NaNO3 supplementation elevated plasma NO3− (32.3±5.6 to 379.8±56.7μmol/L) and nitrite (192.2±15.0 to 353.1±38.7 nmol/L), improved 6MWT distance (387±26 to 425±24 m), peak calf blood flow (BFPeak, 11.6±1.5 to 14.1±1.5 mL/100 mL tissue/min), and peak calf vascular conductance (VCPeak, 11.1±1.3 to 14.2±1.5 mL/dL tissue/min/mmHg, P<0.05 for all). Moreover, improvements in 6MWT distance correlated with calf BFPeak (r=0.70) and VCPeak (r=0.61, P<0.05 for both). Placebo supplementation did not change any of the outcome measures (P=0.22 to 0.92). Neither NaNO3 nor placebo supplementation changed total calf blood flow (P=0.11) or conductance (P=0.18). These data demonstrate that eight weeks of inorganic NO3− supplementation elicits a clinically‐significant improvement in exercise tolerance which correlated to improvements in blood flow and vasodilator function in the lower limbs of patients with PAD.Support or Funding InformationThis study was supported by the American Heart Association 13GRNT16490002 (D.P.C.) and National Institutes of Health Clinical and Translational Science Award U54TR001356.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise Induces Depot‐Specific Adaptations to White and Brown Adipose Tissue
Authors: Baer Lisa A. , Lehnig Adam C. , Dewal Revati S. , Kitching Kathryn M. , Sindeldecker Devin A. , Goodyear Laurie J. , Stanford Kristin I. 
Published: June 2021

Exercise has profound effects on whole body metabolism through adaptations to various tissues including adipose tissue. Several recent studies have investigated exercise‐induced adaptations to two white adipose tissue (WAT) depots, inguinal WAT (ingWAT) and perigonadal WAT (pgWAT), and one brown adipose tissue (BAT) depot, interscapular BAT (iBAT), and shown that each adipose tissue (AT) depot has a distinct response to exercise. Here, we investigated the effects of exercise on each of the 14 AT depots in the body. Ten week old male C57BL/6 mice housed in static cages (sedentary) or were given open access to a running wheel (exercise‐trained) for 3 weeks, and each adipose depot was removed. Exercise increased mitochondrial activity in ingWAT, and pgWAT, and decreased mitochondrial activity in iBAT. Genes and proteins involved in glucose metabolism were upregulated with exercise in ingWAT, and decreased in iBAT, anterior subcutaneous WAT (asWAT), and retroperitoneal WAT (rpWAT). Exercise increased genes and proteins involved in fatty acid oxidation in pgWAT, iBAT, asWAT, cervical BAT (cBAT) and perirenal WAT (prWAT). These data indicate that each adipose tissue depot has a unique response to exercise. Identifying the depot specific adaptations to adipose tissue in response to exercise is essential to determine how adipose tissue contributes to the overall beneficial effect of exercise.Support or Funding InformationNational Institutes of Health Grants R01‐HL138738 and K01‐DK105109This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Moderate Intensity Endurance Exercise Training Increases Muscle Glycogen Content but Does Not Alter Substrate Oxidation in C57BL6 Mice
Authors: Fuller Scott , Simon Jacob , Huang Tai‐Yu , Batdorf Heidi , Scott Matthew , Waskom Callie , Essajee Nabil , Burke Susan , Collier Jason , Noland Robert 
Published: June 2021

INTRODUCTIONAerobic exercise training induces a range of desirable cardiovascular and metabolic adaptations but questions remain regarding the minimum thresholds of intensity, duration, and frequency of training required to elicit measurable changes in health outcomes. We examined the effects of a moderate intensity treadmill endurance training protocol in mice in order to determine whether this intensity level would induce changes in body composition and serum parameters. Furthermore, we investigated the extent to which any such changes would be accompanied by similar changes in muscle and liver substrate oxidation in an effort to better characterize the suite of metabolic adaptations that occur in response to moderate intensity exercise.METHODS20 male C57BL6 mice, approximately 12 weeks of age, were randomly assigned to either an exercise (EX) or sedentary (CON) group. All animals were maintained on low‐fat (13%) rodent chow (LabDiet 5001) and group housed. The EX group underwent a 6‐week program daily treadmill exercise at speeds no greater than 20 meters/min at an incline of 5°. Moderate‐intensity training sessions elicited a 50% increase in circulating lactate, but remained below a lactate threshold level. Body composition was measured weekly by NMR. Mice were euthanized following the cessation of the exercise training protocol. Muscle and liver tissues were collected and substrate oxidation was assessed using 14C labeled substrates. Glycogen content was assayed in liver and quadriceps muscle. Serum parameters were also assessed.RESULTSThe EX group exhibited reduction in body weight and fat mass. Glycogen storage in muscle was significantly increased (p<0.05) by exercise training, whereas intramuscular triglycerides were decreased (p<0.05). There were no statistically significant changes observed in pyruvate, leucine, palmitate, or lignocerate oxidation between the groups, which was supported by a relative lack of changes in gene/protein expression of relevant pathways.CONCLUSIONA moderate intensity 6‐week treadmill endurance exercise program was sufficient to induce a set of “traditional” training adaptations (reduced body weight and fat mass, increased glycogen); however, the stimulus was not sufficient to alter substrate oxidative capacity in skeletal muscle. Collectively these data suggest that in order for exercise training to induce remodeling of substrate metabolism pathways at a molecular level, protocols using higher intensities may be required.Support or Funding InformationThis work was supported by NIH R01 DK103860‐01 (R.C.N.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscular Strength in Well Healed Burn Survivors is Similar to Controls
Authors: Jaffery Manall , Romero Steven , Moralez Gilbert , Kennedy Naomi , Crandall Craig 
Published: June 2021

Recovery from severe burn injuries involves prolonged hospitalization and accompanying bed rest. Additionally, burn survivors are often physically inactive for years after recovery. Inactivity leads to reduced muscle cross sectional area and a reduction in muscular strength. Previous studies have shown that lower body muscular strength is decreased 6 months after discharge from the hospital in burn survivors. However, it is unknown whether well‐healed burn survivors regain the loss of muscular strength by two years post burn injury.PurposeUsing peak torque per body weight (tq/bw) as an indicator of muscular strength, the purpose of this study was to test the hypothesis that muscular strength is reduced in well healed burn survivors compared with non‐burned control subjects.MethodsPeak tq/bw was assessed during leg extension at 90°/sec and 120°/sec using Biodex isokinetic dynamometer in nine non‐burned adults (4 females; age 34 ± 9 years; height 172 ± 19 cm; mass 81 ± 24 kg; mean ± SD) and 19 burn survivors (6 females; age 39 ± 13 years; height 172 ± 10 cm; mass 80 ± 22 kg; mean ± SD). Average body surface area burned was 49 ± 23% (range: 16 – 87%). Subjects were at least two years post burn injury.ResultsNeither tq/bw at 90°/sec (controls: 57.4 ± 16.4 %; burn survivors: 60.4 ± 17.9 % P = 0.6) nor tq/bw at 180°/sec (controls: 49.5 ± 18.8 %; burn survivors: 47.9 ± 12.8 % P = 0.8) differed between groups.ConclusionsThese data suggest that by at least two years post burn injury, burn survivors achieve similar levels of leg muscular strength as non‐burned individuals.Support or Funding InformationFunding provided by the National Institute for HealthThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identification and Characterization of TSSK6 Activating Co‐chaperone (TSACC) in Skeletal Muscle
Authors: Deluna Jonnaly , Waddell David 
Published: June 2021

Skeletal muscle atrophy is a physiological condition that is caused by a variety of conditions, including immobilization, denervation, spinal cord injury and aging and results in decreased muscle size and strength. In order to better characterize the molecular genetic events of neurogenic atrophy, the gastrocnemius muscle was isolated from mice following 3 days and 14 days of sciatic nerve denervation. The gene expression profile in the denervated muscle tissue was then analyzed by microarray and compared to control muscle tissue in order to identify novel neurogenic atrophy‐induced genes. The microarray data revealed for the first time that TSSK6 Activating Co‐chaperone (TSACC) is expressed in skeletal muscle and is significantly induced in response to denervation. To confirm that TSACC is expressed in muscle cells, we cloned the predicted TSACC cDNA from muscle cells, as well as a novel TSACC splice variant that contains an additional exon. Furthermore, quantitative PCR (qPCR) was used to assess TSACC expression levels in both proliferating and differentiated muscle cells and the results demonstrate that TSACC expression levels are relatively low in proliferating myoblasts, but show significantly elevated expression in differentiated myotubes. In order to characterize the transcriptional regulation of TSACC, fragments of the proximal promoter located immediately upstream of the start of transcription were cloned and fused to a reporter gene. The reporter plasmids were then transfected into C2C12 mouse muscle cells in combination with myogenic regulatory factor (MRF) expression plasmids, which resulted in significant activation of reporter gene activity. Interestingly, there are several predicted MyoD binding elements in the proximal promoter region of the TSACC gene further suggesting that TSACC may be regulated by muscle specific transcription factors. The discovery that TSACC is induced in response to neurogenic atrophy helps further our understanding of the molecular genetic events of muscle atrophy and may eventually lead to the identification of new therapeutic targets for the treatment and prevention of muscle wasting.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants to D.W.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mitochondrial Respiration In Skeletal Muscle Mitochondria From Desert Pupfish Suggests Limitation Of Metabolic Substrates As A Mechanism For Paradoxical Anaerobism
Authors: Hillyard Stanley , Jastroch Martin , van Breukelen Frank 
Published: June 2021

Skeletal muscle mitochondria were isolated from desert pupfish (Cyprinodon spp) that were acclimated to ecologically relevant temperatures of 28 °C (M28) and 33 °C (M33). The respiratory control ratio (RCR) of M33 pupfish was ~2.6X lower than that of M28 pupfish, initially suggesting mitochondria were damaged by the warmer temperature. However, state 4 respiration was below expected values in both M28 and M33 pupfish suggesting little proton leak. Further, membrane potential was lower in the M33 pupfish than M28 pupfish and did not change with assay temperature. These data suggested a reduced proton motive force in M33 pupfish. Analyses of respiration as a function of membrane potential suggest a block in substrate utilization in M33 pupfish. M33 pupfish also experience reduced production of reactive oxygen species (ROS) from the Q site of complex I. Taken all together, the data suggest pupfish may be limiting mitochondrial use to avoid ROS production by restricting access of substrates to the mitochondrion. These results are consistent with our measurements of oxygen consumption in intact fish. Specifically, fish acclimated to 33 °C demonstrate extended periods of paradoxical anaerobism in which oxygen consumption is absent despite the presence of oxygen.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CD44v9 and Cystine‐Glutamate Transporter xCT Potentiate the Defense Against ROS to Allow for Effective Healing in Response to Gastric Injury
Authors: Teal Emma L. , Chakrabarti Jayati L. , Steele Nina , Sundaram Nambirajan , Hawkins Jennifer , Wang Jiang L. , Helmrath Michael A. , Diwan Tayyab L. , Zavros Yana L. 
Published: June 2021

BackgroundCluster‐of‐differentiation gene 44 (CD44) is an alternatively spliced cell surface protein that coordinates normal as well as metaplastic epithelial cell proliferation and migration. CD44 variant isoform 9 (CD44v9) is spliced by the epithelial cell‐type‐specific splicing regulator ESRP1 and has been shown to emerge transiently during gastric repair. CD44v9 stabilizes the cystine‐glutamate transporter, xCT, which provides defense against reactive oxygen species (ROS) build up and redox imbalance. ROS produced during injury is a criticial event for the development of epithelial apoptosis leading to ulceration.HypothesisCD44v9 stabilizes the xCT transporter to potentiate defense against ROS to establish an environment conducive to efficient wound repair.MethodsAcetic acid injury was induced in C57BL/6 (BL6) mice and then animals were treated with sulfasalazine (SSZ), an inhibitor of xCT‐dependent cystine transport. Mice were anlayzed between 1–30 days post‐injury. Ulcer size was measured, and CD44v9, xCT and ESRP1 expression and histology was anlayzed. Human‐derived gastric organoids from elderly (>55 years) or young (14–20 years) patients were generated. A novel scratch‐wound assay generated from 3D organoids derived from human stomachs and transferred to a 2D gastric epithelial cell monolayer (huGEM) culture was treated with SSZ. Wound closure was measured by images captured during time‐lapse microscopy and changes in CD44v9 and xCT analzyed by immunofluorescence.Results1) CD44v9 and xCT co‐expressing cells emerge at the ulcer margin: In BL6 mice, CD44v9‐xCT co‐expressing cells emerged at the ulcer margin within 3‐days post‐injury. Compared to control mice, BL6 mice treated with SSZ showed impaired wound healing in response to acetic acid injury. A human gastric ulcer tissue array revealed robust expression of CD44v9/xCT co‐expressing cells in the ulcerated tissue. Expression of CD44v9/xCT was not observed in biopsies collected from elderly patients. 2) Sulfasalazine inhibited wound healing in huGEM scratch wound assays: HuGEM cultures exhibited a cellular composition reflective of primary gastric tissue that included the expression of parietal, chief, and mucous neck and pit cells. CD44v9/xCT co‐expressing cells emerged at the wound edge in huGEM cultures in response to a scratch wound. HuGEM cultures treated with SSZ exhibited significantly delayed wound healing in response to a wound.ConclusionCD44v9 and xCT emerge during gastric regeneration which may potentiate defense against ROS to allow for effective healing. Current studies address the loss of CD44v9/xCT mechanism in the aged stomach using huGEM cultures generated from elderly patients.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.