bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle protein synthesis during the early period of resistance training in rat
Authors: Kotani Takaya , Takegaki Junya , Noda Masahumi , Takagi Ryo , Nakazato Koichi , Ishii Naokata 
Published: June 2021

Increase in muscle protein synthesis (MPS) by resistance exercise (RE) has been thought to be caused by increases in translational efficiency (major regulator: mammalian target of rapamycin (mTOR) signaling pathway) and translational capacity (ribosome content).It has been shown that repeated bouts of RE leads to the attenuation of the activation of mTOR signaling and the increase in ribosome content after a bout of RE (Ogasawara et al. 2013). However, it is unknown whether MPS response to RE is also declined when exercise bout is repeated.PurposeTo see if the acclimatization occurs in the response of protein metabolism to exercise during the course of RE , the present study investigated the changes in MPS, mTOR signaling pathway and ribosome content with the increase of RE bout.MethodMale Sprague‐Dawley rats were randomly assigned into three groups: Sedentary (SED), resistance‐trained with 1 bout (1B), 3 bouts (3B). RE protocol consisted of 50 repetitions of maximal isometric contraction of the gastrocnemius muscle elicited by direct electric stimulation under anesthesia. A day recovery period was taken between each bout. Muscle samples were collected 6h after the last RE session.ResultsAmount of puromycin‐labeled peptides was larger in trained groups than in SED, but no significant difference was seen between 1B and 3B. Posphorylation of p70S6K was larger in trained groups than in SED, and significantly larger in 1B than in 3B. By contrast, ribosomal RNA content was larger in trained groups than in SED, and significantly larger in 3B than in 1B.ConclusionMPS after repeated bouts of RE was unchanged from that after a single bout in spite of the attenuated response of mTOR signaling. This may be caused by the compensatory increase in ribosome content with the increase in the exercise bout.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Defining Acceptable Cold‐Water Immersion Times for the Treatment of Exertional Hyperthermia When Rectal Temperature Measurements are not Available
Authors: Poirier Martin P. , Notley Sean R. , Gagnon Daniel , McGinn Ryan R. , Friesen Brian J. , Flouris Andreas D. , Kenny Glen P. 
Published: June 2021

Exertional hyperthermia is most effectively treated with immediate whole‐body cold‐water immersion to rapidly cool the body to the safe rectal temperature (Tre) of 38.6°C, which is the cooling limit recommended to negate any risk associated with overcooling hyperthermic individuals. However, the safe use of cold‐water immersion is reliant on real‐time measurement of Tre to identify the appropriate immersion time, which is often unavailable in emergency situations. The purpose of this study was to determine appropriate immersion times for the immediate treatment of exertional hyperthermia for a range of water temperatures (2°C to 26°C) and following a treatment delay (20 min and 40 min) to guide emergency management in the absence of continuous Tre measurements. Data were extracted from seven published studies (143 experimental sessions) involving 79 participants (65 males, 14 females; age: 26 ± 6 years; height: 177 ± 9 cm; weight, 76.9 ± 13.0 kg; body fat: 17.3 ± 6.9%; peak oxygen consumption: 56.9 ± 7.9 mL/kg/min). In each study, individuals rendered hyperthermic (Tre 39.5–40.0°C) during exercise in the heat were treated immediately with immersion in water at 2°C, 8°C, 14°C, or 26°C. Separate study conditions assessed cold‐water immersion (2°C) following a 20 and 40 min treatment delay. From these data, receiver operating characteristics curves were used to define acceptable cooling times (time for Tre to reach 38.6°C) for each condition (all p<0.05). Our analysis revealed that 9 min would be the recommended cooling time for immersion in water temperatures ranging from 2°C to 8°C (average sensitivity at 2°C: 0.84, average sensitivity at 8°C: 0.82; average specificity at 2°C: 0.82, average specificity at 8°C: 0.96). For immersion in water temperatures between 14°C and 20°C, the suggested cooling time was 10 min (average sensitivity: 0.80; average specificity: 0.76), whereas it was 14 min at 26°C (average sensitivity: 0.73; average specificity: 0.79). When the gold standard water temperature of 2°C is available, a cooling time of 11 min is recommended if immersion is delayed between 20 and 40 min (average sensitivity: 0.84; average specificity: 0.94). Our results provide the first clinical guidance to health practitioners for the emergency treatment of exertional hyperthermia using water immersion at a range of water temperatures and following a treatment delay when Tre measurements are unavailable.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (grant held by Dr. Glen P. Kenny).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Growing Evidence that Periderm is Essential for Orofacial and Epidermal Development
Authors: Schutte Brian C. 
Published: June 2021

Orofacial clefting is one of the most common birth defects, affecting about 1/700 births world wide. The cause of orofacial clefting is complex, including multiple genetic and environmental factors. To date, genome wide association studies have identified 36 loci that contribute risk, and linkage studies have identified the gene involved in 249 rare syndromes. However, these loci still only account for a fraction of the overall heritability of orofacial clefting. To determine the “missing heritability”, we need a better understanding of the pathological mechanisms that lead to orofacial clefts. Recent human and animal genetic studies suggest that proper periderm development is one essential pathway during palatogenesis. The periderm is the superficial layer of squamous epithelial cells that covers the ectoderm of mammalian embryos. During palatogenesis, the periderm covering the medial edge of the palatal shelves must degenerate at a precise moment to allow palatal fusion. If the periderm degenerates too early, or too late, the palatal shelves may not fuse, leading to a cleft palate. Based on mutant mouse studies, 20 genes have been identified as essential for proper periderm development. Significantly, DNA variation in 13 of the 20 genes causes and/or contributes risk for orofacial clefting in humans, including transcription factors (IRF6, GRHL3, TP63, TBX1, TFAP2A) and cell signaling molecules (FGF10, FGFR2, NOG, RIPK4, TGFB3). Several of these genes were also shown to be required for development of the enveloping layer during zebrafish embryogenesis. Like the mammalian periderm, the enveloping layer is the superficial layer of epithelium that surrounds the zebrafish embryo. The apparently conserved functions of these genes in periderm and enveloping layer has allowed the development of robust functional assays in zebrafish for testing potentially pathogenic mutations found in patient with orofacial cleft. Moreover, the significance of this set of genes is not limited to development, as somatic mutations and altered expression has been associated with cancer, especially squamous cell carcinoma.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
LMCD1 acts as a coactivator for E2F1 in CDC6 expression to promote human aortic smooth muscle cell replication and atherogenesis
Authors: Singh Nikhlesh K. , Janjanam Jagadeesh , Zhang Baolin , Mani Arul M. , Traylor James G. , Orr A. Wayne , Rao Gadiparthi N. 
Published: June 2021

In exploring the mechanisms underlying restenosis, we have identified LMCD1 as a highly responsive gene to thrombin in human aortic smooth muscle cells (HASMCs). Depletion of LMCD1 levels inhibited human but not murine vascular smooth muscle cell replication. LMCD1 via interacting with E2F1 mediates thrombin‐induced CDC6 expression in the regulation of HASMC replication. Thrombin‐induced LMCD1 and CDC6 expression exhibited a requirement for PAR1‐mediated Gαq/11‐dependent PLCβ3 activation. In addition, the expression of LMCD1 was highly induced in SMC of human atherosclerotic lesions and correlated with CDC6 expression and replication marker Ki67. Furthermore, the LMCD1 and SMCαactin‐positive cells were found to possess higher cholesterol levels in the atherosclerotic lesions. Thus, these findings for the first time show that LMCD1 via acting as a coactivator for E2F1 in CDC6 expression modulates HASMC replication and hence promotes human atherogenesis.Support or Funding InformationThis work was supported by grants HL069908 and HL103575 (to GNR) and HL098435 and HL133497 (to AWO) from NHLBI of NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evidence for Activation of Host Cell Protein Kinase C Signaling from Proteomics Analysis of Coxiella burnetii‐Infected THP‐1 Cells
Authors: Funk Cornelius Joel , Jackson Christa 
Published: June 2021

The bacterium Coxiella burnetii can infect cells found in the human lung and cause a respiratory tract infection that manifests as Q‐fever disease. The acute infection typically results in mild flu‐like symptoms that are treatable with antibiotics; however, chronic infections can lead to endocarditis, hepatitis, or death, if left untreated. Bacteria enter alveolar macrophages within a phagosome, but rather than being destroyed by the hydrolytic lysosomal enzymes, C. burnetii induces the host cell to develop a lysosome‐like organelle designated the parasitophorous vacuole (PV) where replication takes place. The PV grows in size to accommodate the increasing number of replicating cells before the bacterial cells are released as the host cell is destroyed. The objective of this study was to identify Protein Kinase C (PKC) substrates and other activated cell signaling pathways using proteomics. Proteins from infected and uninfected THP‐1 cell samples were labeled using isobaric tagging and analyzed using an ion trap mass analyzer (LC‐MS/MS) to identify proteins and post‐translational modifications that were altered during infection. Previous work indicated that C. burnetii infections lead to activation of several Protein Kinase C (PKC) isoforms, which in turn lead to phosphorylation of the PKC substrate MARCKS. Analysis of infected THP‐1 cell samples identified two additional PKC substrates that were phosphorylated during the infection, MARCKSL1 (a MARCKS‐related protein) and ABCA1 (a cholesterol efflux protein). Additional analysis indicated that both proteins were upregulated during the infection at the gene and protein level using qPCR and immunoblotting, respectively. These results provide additional evidence that PKC cell signaling is altered during C. burnetii infection of the host cell and may provide insight into critical events that can be targeted for inhibition of the infection.Support or Funding InformationSupported by a grant from Arkansas INBRE (NIH NIGMS P20 GM103429).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Human Macrophage Derived Myeloperoxidase Exacerbates Nonalcoholic Steatohepatitis Disease (NASH) in Diet‐induced Obesity
Authors: Katunga Lalage A. , Franke Jacob D. , Schulte Kevin A. , Ford David A. 
Published: June 2021

BackgroundHepatic infiltration of polymorphonuclear leukocytes (PMNs) is a key driver of pathogenesis in non‐alcoholic steatohepatitis (NASH). Lipotoxicity arising from elevated free fatty acids in NASH is postulated to advance PMN activation and recruitment. Myeloperoxidase (MPO), a PMN‐derived enzyme mechanistically linked to oxidative stress (ROS) in inflammation, may contribute to this feedback. Chlorinated fatty acids (2‐ClFAs) are an MPO by‐product produced when HOCl targets plasmalogen phospholipids. 2‐CIFAs induce PMN activation, adhesion and ROS mediated cellular damage. In human patients, a strong positive correlation between MPO expressing cells and severity of NASH has been observed. However, mouse macrophages lack MPO and this is a critical limitation of current models. As a result, the contribution of MPO to NASH remains poorly understood.MethodsTo investigate the role of MPO in NASH, C57Bl/6J mice expressing macrophage transgenic human MPO (hMPOTg) were fed a 40% high fat (HF) diet for 10 weeks. At the end of the study biomarkers of hepatocellular damage and PMN infiltration were measured. Alterations in lipid species were detected using electrospray ionization tandem mass spectrometry (ESI‐MS/MS) lipidomics in order to elucidate contributing lipids to NASH.ResultsHere we show hMPOTg is associated with significant alteration in the hepatic lipidome, increased infiltration of PMNs, levels of MPO lipid by‐products and exacerbated hepatic steatosis. HF fed hMPOTg mice showed greater weight gain and hepatomegaly. Increased infiltration of PMN in hMPOTg HF livers was supported by immunohistochemistry and PCR analysis of PMN biomarkers. Significantly higher triglyceride levels were detected in hMPOTg HF fed plasma and livers. Major hepatic lipid species of cholesterol esters, phosphatidylcholine, and phosphatidylserine were also significantly altered. Systemic pro‐inflammatory 2‐CIFA levels were increased in HF fed hMPOTg.ConclusionTogether, our results highlight the significant contribution of hMPO to hepatic lipid homeostasis. MPO is currently exploited as a biomarker and therapeutic target in cardiovascular disease. Expanding our understanding of MPO may extend the benefits of similar therapeutic strategies to patients suffering from NASH and metabolic syndrome.
Sympathetic nerve response to optogenetic inhibition of PVN‐RVLM neurons in anesthetized rats with heart failure
Authors: Hanai Eri , Kumada Nao , Watanabe Tatsuo , Koba Satoshi 
Published: June 2021

Central neuronal cell groups that underlie enhanced sympathetic nerve activity (SNA) in heart failure (HF) have not been identified. Here, we tested the hypothesis that paraventricular hypothalamic nucleus (PVN) neurons that send axonal projections to the rostral ventrolateral medulla (RVLM) mediate this abnormality by examining the effect of optogenetic inhibition of PVN‐RVLM neuron activity on renal SNA (RSNA) in anesthetized rats after myocardial infarction (MI). More than one week after left coronary artery ligation to induce MI, rats received bilateral microinjection into the PVN of an adeno‐associated virus (AAV) vector that encodes reporter protein mcherry (control‐MI rats, N=6) or the light‐activated inhibitory opsin Archaerhodopsin‐eYFP (ArchT‐MI rats, N=12). The AAV vector encoding ArchT‐eYFP was also bilaterally microinjected into the PVN of the sham‐operated rats (ArchT‐sham rats, N=6). More than three weeks later, intermittent bouts (1‐ to 4‐sec stimulation to non‐stimulation) of photostimulation (532 nm wavelength, 5 mW) for 1 min were bilaterally provided to the RVLM of rats anesthetized with a mixture of urethane and α‐chloralose. The RSNA responses to 12 optogenetic stimulations were superimposed on one another and averaged. The superimposing analysis showed that 1‐sec photostimulation significantly (P<0.05) changed RSNA from baseline in ArchT‐MI rats while this stimulation had no effect in control‐MI or ArchT‐sham rats. During the early 500‐msec period of 1‐sec photostimulation, the RSNA changes from baseline were not significant or did not differ among rat groups (+7 ± 6, +4 ± 15, and +14 ± 10% for ArchT‐MI, control‐MI, and ArchT‐sham rats, respectively). During the late 500‐msec period, on the other hand, a significant RSNA inhibition from baseline was detected in ArchT‐MI rats (−35 ± 10%), which was significantly different from the RSNA changes in control‐MI and ArchT‐sham rats (+6 ± 9 and +15 ± 11%). Left ventricular end‐diastolic pressure was increased in rats after MI [+7 ± 3 mmHg, 40 ± 5% of infarct size (IS)] as compared to sham‐operated rats (+2 ± 0 mmHg, 0 ± 0% of IS), indicating heart dysfunction in rats after MI. Taken together, we suggest that dysfunction of PVN‐RVLM neurons underlies enhanced SNA in HF.Support or Funding InformationSupported by JSPS KAKENHI 15H05367 (SK) & 16K15190 (SK), the Nakatomi Foundation grant (SK), and the Takeda Science Foundation grant (SK).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Salt Diet Influences Endothelin‐1 Signaling in Renal Sensory Nerves
Authors: Becker Bryan K. , Speed Joshua S. , Pollock David M. 
Published: June 2021

Renal denervation is an effective anti‐hypertensive treatment in both humans and many animal models. However, it is unclear if the benefits of renal denervation are due to severing of the efferent (motor) nerves, afferent (sensory) nerves, or both. Recently, we reported that total renal denervation lowered blood pressure and global sympathetic tone in a model of endothelin B receptor (ETB‐R) deficiency without affecting renal excretory function or sodium balance suggesting a role for the afferent nerves in mediating hypertension and sympathetic tone in this model. High salt diet and endothelin‐1 signaling sensitize afferent activity, but the long‐term consequences and mechanisms of afferent sensitization are still relatively unknown. Thus we hypothesized that changes in salt diet would alter the gene expression profiles in renal afferent nerves following a high or low salt diet or endothelin receptor antagonist treatment. We isolated dorsal root ganglia (DRG) that contain the cell bodies of renal afferent nerves from Sprague‐Dawley rats fed either normal salt (NS, 0.49% NaCl), low salt (LS, 0.04% NaCl), or high salt (HS, 4.0% NaCl) for three weeks, or normal salt with 10 mg/kg/d ABT‐627 (ETA‐R antagonist) or 30 mg/kg/d A‐192621 (ETB‐R antagonist) for one week for qRT‐PCR analysis. Rats fed HS diet had significantly elevated expression of brain‐derived neurotrophic factor compared to NS (5.9 ± 1.8 relative to NS; p=0.04, n=3–4/group) indicating that HS diet activates renal afferent nerves as has been previously reported. Animals fed LS diet were not significantly different than NS. Neither salt diet had a significant effect on endothelin‐1 expression in DRG. Surprisingly, both LS and HS diets decreased the expression of both ETA‐R (0.7 ± 0.01 relative to NS p=0.1 and 0.4 ± 0.2 relative to NS p=0.04; respectively) and ETB‐R (0.5 ± 0.03 relative to NS p<0.001; and 0.5 ± 0.1 relative to NS p<0.001; respectively). Antagonism of ETA‐R resulted in a 2.0 ± 0.3 fold increase in endothelin‐1 expression in DRG compared to NS (p=0.02), while ETB‐R blockade had no effect (p=0.99) compared to NS, suggesting that ETA‐R activity may suppress endothelin‐1 expression in renal afferent nerves. These data suggest that salt diet influences activity of renal afferent nerves and that endothelin‐1 signaling in afferent nerves may be important modulators of activity.Support or Funding InformationT32HL007457 to BKB; K99HL127178 to JSS; and P01HL136267 to DMPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Relationship Between Heart Rate Variability (HRV) and Anxiety Through Music Intervention
Authors: Tolley Annalise Julia , Vick Robert Stephen 
Published: June 2021

BackgroundResearch shows that lower heart rate variability (HRV) is associated with multiple health risks, including early mortality, congestive heart failure and mental illness. Research on the relationship between HRV and anxiety has been inconclusive but should be studied, as HRV may be a noninvasive indicator of overall mental health. Music has been used as an inexpensive intervention method to significantly lower self‐reported anxiety in multiple populations.ObjectiveTo determine the strength of the possible relationship between anxiety and HRV with music intervention.Subjects and MethodsA within‐subjects experimental design was used with undergraduate students (n=32). Self‐reported anxiety used STAI, followed by the collection of seven minutes of baseline EKG data. Seven minutes of pre‐selected, “relaxing” music was played (intervention) while physiological indices were again collected. The STAI was re‐administered.ResultsAfter music intervention, significant reduction in anxiety (p<0.001) and heart rate was demonstrated (p<0.01), with a significant increase in RR (p<0.01), SDRR (p<0.01), and pRR50 (p<0.01). No correlation was found between the change in anxiety and physiological indices (p=0.737).ConclusionsUndergraduate students may benefit from music intervention, as music significantly improved self‐reported anxiety and physiological anxiety, as measured by STAI score and HRV, respectively. However, these improvements seemed to occur independently, thus decreasing the strength of the proposed relationship between HRV and anxiety in the literature. Elon University IRB #17‐083.Support or Funding InformationResearch supported by Elon University Undergraduate Research Program (URP) and Elon College Fellows (ECF) program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.