bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial SIRT1 expression following endurance and resistance exercise training in young and old rats
Authors: Cross Whitney L. , Roby Mackenzie A. , Deschenes Michael R. , Harris M. Brennan 
Published: June 2021

Previous studies indicate a link between caloric restriction, SIRT1 expression, and longevity. It has been suggested that the metabolic stress of exercise may also alter SIRT1 expression. Therefore, we evaluated the effects of two different modes of exercise training on myocardial SIRT1 protein expression in young and old rats. In the first study, young (8 mo) and old (24 mo) Fisher 344 rats were subjected to a progressive treadmill training program for 10 wks ending at 60 min/day, 15 m/min, 0% grade. Myocardial SIRT1 expression was not significantly different (P>0.05) between young and old rats. However, endurance training resulted in a significant (P<0.05) decrease in myocardial SIRT1 protein expression. In the second study, young (5 mo) and old (22 mo) Fisher 344 rats were resistance trained by ladder climbing for 8 wks. Animals began by lifting 50% body weight and ended the training protocol lifting 276±6% body weight (young) and 141±12% body weight (old). Again, we observed no effect of age on myocardial SIRT1 expression. However, in contrast to endurance training, resistance training resulted in no significant (P>0.05) change in SIRT1 expression. The results of this study demonstrate that exercise‐induced changes in myocardial SIRT1 expression are dependent on the mode of training.Supported by Borgenicht Program for Aging Studies and Exercise Science (MBH), AHA SDG 0430157N (MBH), and the NIA (MRD).
Protein and mRNA expression of mitochondrial transcription factors TFB1M, TFB2M and TFAM in elite athletes
Authors: Sundberg Carl Johan , Norrbom Jessica , Rundqvist Helene , Wallman Susanna , Jansson Eva , Gustafsson Thomas 
Published: June 2021

The aim of the present study was to investigate mRNA and protein levels of mitochondrial transcription factors Tfam, TFB1M and TFB2M in individuals with high oxidative capacity (elite athletes) compared to normally trained individuals, as well as the effect of 5 weeks of exercise in healthy males.Method: Skeletal muscle biopsies were obtained from the vastus lateralis muscle at rest from 12 males with high oxidative capacity, 9 moderately trained male controls and 12 healthy males before and after 10 days and 5 weeks of one‐legged knee extension exercise. One leg exercised with restricted blood flow (R‐leg), the other with non‐restricted blood (NR‐leg) flow.Results: mRNA expression of TFB1M and TFB2M was increased after 10 days and 5 weeks of exercise in the R‐leg. Moreover, higher mRNA expression of both TFB1M and TFB2M was detected in elite athletes compared to moderately active individuals. No differences in TFAM mRNA were observed.Conclusion: This suggests that metabolic perturbation, induced by regular contractile activity, or a higher oxidative status have long‐term effects on steady state mRNA expression of TFB1M and TFB2M but not on Tfam. Protein analyses could not detect any differences in TFB1M and TFB2M between elite athletes and moderately active individuals. However, TFAM protein expression was significantly higher in the elite athletes.
12‐weeks of Aquatic Exercise Training modifies mTOR signaling following Essential Amino Acid + Carbohydrate Ingestion in Older Subjects
Authors: Christian Dreyer Hans , John Drummond Micah , Fujita Satoshi , Rasmussen Blake , Volpi Elena 
Published: June 2021

Essential amino acid (EAA) ingestion can stimulate muscle protein synthesis in young and older subjects. In older subjects however, the addition of carbohydrate (CHO) (EAA+CHO) blunts the anabolic response as compared to young subjects and may be due to dysregulation of the insulin signaling pathway. Recent evidence shows that a single bout of aerobic exercise, performed within 24hrs, restores the anabolic response in older muscle following insulin infusion.PURPOSE: To determine if 12 weeks of aquatic exercise training would similarly maintain the EAA+CHO‐induced anabolic response in older muscle.METODS: Immunoblotting methods were used to determine mTOR signaling, at 1 and 2h post EAA + CHO ingestion pre and post‐training.RESULTS: Our preliminary results from 5 older subjects demonstrate that mTOR phosphorylation is more robust at 1hr post EAA+CHO ingestion following 12 weeks of aquatic training (P<0.05) while there was no change in the phosphorylation status of Akt, S6K1, 4E‐BP1, and eEF2 after training.CONCLUSIONS: Our preliminary findings suggest that mTOR phosphorylation is significantly greater 1hr post EAA+CHO ingestion following 12 weeks of aquatic exercise training as compared to pre‐training. This may provide potential evidence for a beneficial exercise training adaptation which improves the ability of older individuals to respond more efficiently to anabolic nutrients.This work was supported by a Pepper Pilot Project award
Cyclooxygenase mRNA expression in human patellar tendon at rest and after exercise
Authors: Carroll Chad C , Jemiolo Bozena , Trappe Scott W , Døssing Simon , Kjaer Michael , Magnusson S Peter , Trappe Todd A 
Published: June 2021

Exercise has been shown to acutely elevate several metabolic processes in tendon tissue, many of which are regulated by the cyclooxygenase (COX) enzymes. We measured the expression levels of COX‐1 (variants 1 and 2), COX‐2, and the recently discovered intron 1‐retaining COX‐1 variants (COX‐1b1, ‐1b2, ‐1b3) at rest and following resistance exercise (RE). Patellar tendon biopsy samples were taken from six individuals (3M, 3F) before and 4h following a bout of RE (3 sets of 10 repetitions at ~70% of 1RM) and from a separate six individuals (3M, 3F) before and 24h following RE and analyzed using real‐time RT‐PCR. The COX‐1 variants were the most abundant COX mRNAs before exercise and remained unchanged (p>0.05) following exercise. COX‐2 was also expressed in tendon at rest and was unchanged (p>0.05) following exercise. The intron 1‐retaining COX‐1 variants were not detectable in tendon tissue before or after exercise. Compared to our previous work in quadriceps skeletal muscle, the patellar tendon expressed much higher levels of COX‐1 and COX‐2, although the overall COX mRNA expression patterns were similar in skeletal muscle and tendon (COX‐1v2 > COX‐1v1, P<0.05; COX‐1:COX‐2 ≅ 4:1). These results suggest both COX‐1 and COX‐2 are constitutively expressed at relatively high levels in human patellar tendon and are likely targets of COX inhibiting drugs at rest and following physical activity.NIH R01 AG020532 (TT)
Evaluation of hemodynamic renal in the isolated perfused rat kidney after nitric oxide blockade
Authors: Fiorino Patricia , Farah Vera Azevedo , Darini Kalebe G , Araujo Iara Cristina , Leite Ana Paula Oliveira , Fonteles Manasses Claudino 
Published: June 2021

Chronic administration of the nitric oxide synthase inhibitor L‐NAME causes arterial hypertension and renal injury. The purpose of this study was to evaluate in hypertensive animals induced by L‐NAME the renal hemodynamic and renal function using isolated perfused kidney model. The rats (n=5, each group) were divided in: 1)Normotensive (Nt), without treatment and 2)Hypertensive group: L‐NAME administration in the drinking water (600 mg/L) during 7 days (H7). L‐NAME treatment induces an increase in arterial blood pressure (143 +/− 2.2 vs. 105+/− 1.8 mmHg, H7 vs. Nt). Isolated kidneys were perfused with Krebs‐Henseleit solution containing 6g of previously dialysed bovine serum albumin for 60 min. The treatment increased the perfusion pressure (Nt=103.4 +/−1.2; H7=143+/−7.66 mmHg), and renal vascular resistance (Nt=4.5+/−0.51; H7=14.01+/−0.7 mmHg). These alterations were accompanied by a reduction of the urinary flow (Nt=0.16+/−0.01; H7=0.09+/−0.02 mL g(‐1) min(‐1)) and glomerular filtration rate (Nt=0.84+/−0.075; H7=0.19+/−0.032 mL g(‐1) min(‐1)). These finding showed that NO generated within the kidney contributes to the regulation of renal vascular tone in rats. In conclusion, our data suggests that NO inhibition induces dramatic changes in renal function demonstrated in the ex‐vivo kidney perfusion.Financed by CNPq and MackPesquisa, Brazil
Real‐time interactive fusion of physical/electronic auscultation simulation and 3D CT/MRI‐based anatomical modeling applied to training in lung sounds detection, discrimination and classification
Authors: Canby Craig , Hisley Kenneth , Kolbinger Gregory , Stanton Charles , Vardaxis Vassilios , Donald Matz , Khan Makdoom 
Published: June 2021

Objective: To test the instructional effectiveness of simultaneous coupling of the spatial detection, discrimination and classification of simulated lung sounds to real‐time viewpoint tracking of displayed digital 3D anatomical models over the current method of auscultation alone. Methods: An integration of a computer‐based clinical training system comprising two complementary functions: 3D anatomical visualizations, and physiological diagnostic sounds simulation using a physical manikin. These functions are linked in real‐time by the student stethoscope's 3D position/orientation in space on the surface of the manikin. Thus, during any given simulation drill using as input a pre‐defined diagnostic lung sound, a student will sample signs from the manikin and simultaneously view the case's prescribed condition or pathology volumetrically reconstructed and visualized from de‐identified patient MRI/CT image sets carefully selected to represent the given abnormality. Expected results: Active student tracking, perception of diagnostic sounds and visualizations of the corresponding anatomical structures will significantly increase student learning over methods using auscultation without visualization.This research is supported by the Department of Anatomy and the Dean's Office, Des Moines University.
Gαo proteins regulate the α2A adrenergic receptor‐mediated inhibitory effects of epinephrine in the mouse hippocampal CA3 region
Authors: Nelson Brian W , Xu Ke , Goldenstein Brianna , Pribula Jacquline , Luger Elizabeth , Wald Jenna , O'Shea Lorraine , Charbeneau Raelene , Huang Xinyan , Richard Neubig , Doze Van 
Published: June 2021

Activation of α2A adrenergic receptors by epinephrine (EPI) attenuates seizure activity in the rat hippocampal CA3 region. Questions concerning the specific mechanism of this action are whether the α2A receptors are located pre‐ or post‐synaptically, and what subtype of G protein is coupled to this receptor. Evidence suggests that pre‐synaptic terminals of the recurrent axon collateral on pyramidal cells are involved; we hypothesize that the α2A receptors are located pre‐synaptically. We used transgenic mice with knock‐ins of the inhibitory regulators of G‐protein signaling (RGS)‐insensitive G183S Gnai2 allele for either the pre‐synaptic Gαo or the post‐synaptic Gαi2 protein subtype. EPI's anti‐epileptic effects were assessed with electrophysiological recordings in brain slices from control mice, modified Gαo mice, and modified Gαi2 mice.The EC50 of EPI was not significantly different between age‐matched C57BL/6J control and modified Gαi2 mice. In contrast, EPI was significantly more potent (>7‐fold) in the Gαo mice than the littermate controls. These results suggest that the pre‐synaptic Gαo protein and not the post‐synaptic Gαi2 protein mediates EPI's inhibition of hippocampal CA3 epileptiform activity. These findings could lead to new strategies for treating epilepsy. Supported by ND EPSCoR, NSF CAREER 0347259, NSF REU Site 0639227, NIH 5RO1GM039561, NIH P20 RR016741 from the INBRE Program, APS.
Phosphorylation and the Transcription Factor YY1
Authors: Rizkallah raed Mtanis , Hurt Myra M 
Published: June 2021

Yin‐Yang 1 (YY1) is a multifunctional transcription factor that is involved in the regulation of a large array of genes controlling cellular proliferation, differentiation and even apoptosis. Although our knowledge of the events regulated by YY1 has grown significantly over the past decade, we still know little of what regulates YY1 and its functions. YY1 has been previously described as a phosphoprotein. However, only indirect evidence for this has been provided, and the role of phosphorylation in regulating YY1's functions has not been elucidated. Here we provide direct evidence for YY1's phosphorylation by in vivo labeling studies. Additionally we have studied the effect of phosphorylation on purified YY1's affinity to several of its DNA binding sites. Since YY1 is involved in the regulation of replication‐dependent histone genes at the G1/S transition of the cell cycle, we examined YY1 as a possible substrate for cell cycle kinases. We found that YY1 is a substrate for CyclinE/Cdk2 in an in vitro kinase assay. Through site directed mutagenesis, we have identified the phosphorylated amino acid. Phosphorylation of this site was independently confirmed in vivo by Mass Spec analysis of the purified protein. The function of phosphorylation of YY1 at this site is the subject of current research in our lab.This research was supported by a grant from Order of the Eastern Star and FSU College of Medicine.
Upregulation of the alpha7 nAChR in human macrophages is induced by chronic treatment with HIV‐1 envelope protein, gp120
Authors: Lázaro María Isabel , Santiago‐Pérez Laura Iris , Ballester Leo , Román Laura Rodríguez , Azoulay Hilla , Lasalde‐Dominicci José A , González Carlos I 
Published: June 2021

Human immunodeficiency virus type‐1 (HIV‐1) infection is the commonest cause of dementia in adults less than 40 years. The cellular and molecular alterations that result in synaptic dysfunction, neuronal degeneration and cell death due to HIV‐associated dementia (HAD) by HIV‐1 infection appears to be caused by the infection of macrophages, microglia or by stem cells. We examined the effects of gp120 on the upregulation of the alpha7 nAChR expressed in human macrophages. Compared to controls, chronic treatment with gp120 showed a remarkable increase in the expression of the α7 nAChR with an increase in the concentration of gp120. In addition, macrophages chronically exposed to gp120 showed an increase the macroscopic whole‐cell currents compared to controls. After chronic exposure to gp120, macrophages also presented an increase in calcium uptake compared to non‐treated macrophages. Interestingly, experiments in several cell lines showed a similar up‐regulation of the α7 AChRs, suggesting that the up‐regulation could be occurring through a direct mechanism. We are currently conducting polysome analysis in continuous sucrose gradients to determine whether treatment with gp120 enhances the α7 nAChR mRNA association with the translational machinery. This notable up‐regulation of the α7 nAChR induced by the gp120 may be critical to the functional state of macrophages. Our data suggests that the α7 nAChR could be a key player in the HIV pathogenesis.This research work was supported by NIH GM008224, 2R01GM56371–11, NCRR 1S0RR13705 and by NIH SNRP‐U54NS4301 to JAL‐D. Also supported by NIH U54 Award CA96297–03 and NIH S06‐GM008102–3052. M.I.L is supported by RISE Award 2R25GM61151.
Altered Adenosine to Inosine editing in lupus T cell transcriptome
Authors: Dama Laxminarayana 
Published: June 2021

Adenosine to Inosine (A to I) editing induced by adenosine deaminases that act on RNA (ADARs) lead to the specific alteration of the primary sequence of an RNA molecule and its expression. Phosphodiesterase 8 (PDE8), Ubiquitin Carboxyl‐Terminal Hydrolase (UCTH) and Interferon alpha receptor 2 (IFNAR2) play an important role in regulating many cellular functions and their gene transcripts contain known editing sites. Therefore, in the present studies the transcripts of these genes were analyzed for ADAR mediated editing in normal and lupus patients. The principal finding of this study is the altered editing at known A to I editing sites of PDE, UCTH and IFNAR2 gene transcripts of lupus T cells. The second important observation is the occurrence of novel A to I editing sites and hot spots in these gene transcripts of the lupus patients. A third fundamental finding is the compensatory alteration of A to I editing frequencies at hot spots. Based on these results, it is surmised that, such alterations and compensations at selective editing targets in gene transcripts may be due to qualitative and/or quantitative changes in ADAR enzymes. Therefore, transcript editing is a novel unrecognized epigenetic mechanism that contributes to the abnormal expression of genes and, ultimately, impaired immunity in lupus pathogenesis.This work was supported by National Institutes of Health Grant AR48628 (to D.L).
M cell development occurs preferentially in distal small intestinal Peyer's patches in mice lacking B cells (μMT), CCR6, or TRANCE/RANKL
Authors: Freel Kathryn A , Taylor Rebekah T , Butler Betsy R , Kumar Nachiket , Williams Ifor R 
Published: June 2021

Peyer's patches (PP) are inductive sites for generation of mucosal IgA antibody responses in the small intestine (SI). M cells are specialized epithelial cells present in the follicle‐associated epithelium (FAE) of PP that acquire small particulate antigens and convey them to immune cells in the subepithelial dome. The exact molecular signals driving differentiation of FAE enterocytes into M cells have not yet been defined. In wild type (WT) mice, the extent of M cell development is equal in PP throughout the SI. B cell deficient mice (μMT) were previously shown to have smaller PP with fewer follicles and a reduced density of M cells. Whole mount immunofluorescence staining of PP from μMT mice with Ulex europaeus lectin (UEA‐1) labeled with rhodamine reveals a consistent proximal to distal gradient in the extent of M cell development with PP follicles from the proximal third of the SI containing 6.0% of the M cells in WT PP and follicles from the distal third containing 79.0% of the WT level. A proximal to distal gradient was also observed in 2 other mutant mice (CCR6 and TRANCE/RANKL knockout mice) with impaired M cell development. In TRANCE deficient mice no M cells are observed in PP from the proximal third of the SI and the number of M cells in the middle and distal third rises to just 1.9% and 12.3% of WT levels. The existence of a proximal to distal gradient in M cell development in PP from these mutant mice demonstrates that M cell development is a complex process shaped by molecular cues that differ regionally along the SI. The greater reduction in M cells in the proximal PP of the models studied may reflect the later initiation of PP organogenesis and/or the increased density of the enteric microflora in the distal SI.Supported by the NIH (DK‐64730, DK‐64399).
Rapamycin impairs skin γδ T cell function resulting in autophagy
Authors: Jameson Julie , Mills Robyn , Podshivalova Katie 
Published: June 2021

Epithelial tissues provide barrier functions vital to the survival of the organism. To maintain this protective role, there is a complex regulation of epithelial cell proliferation and survival. γδ TCR‐expressing lymphocytes reside within the epithelia where they regulate tissue homeostasis and repair by producing growth factors, cytokines, and chemokines. Chronic nonhealing wounds are a devastating consequence of defective tissue repair. Patients that receive the immunosuppressant Rapamycin for the prophylaxis of acute kidney rejection report an increased incidence of wound healing complications. We hypothesize that rapamycin not only targets allograft‐specific αβ T lymphocytes, but also suppresses skin γδ T cells resulting in defective tissue repair. Rapamycin inhibits the signaling molecule mTOR, a key player in growth factor and cytokine signal reception. We have established a murine model of rapamycin administration in which there is delayed wound repair. Treatment with rapamycin arrests skin γδ T cell proliferation in G1 phase and causes the T cells to undergo autophagy. In addition skin γδ T cells exhibit a defect in TNF‐α production at the wound site. We propose that rapamycin blocks the ability of skin γδ T cells to receive nutrient and growth factor signals resulting in autophagy. This limits the ability of skin γδ T cells to proliferate and negatively impacts their ability to mediate wound repair.Support from Leukemia and Lymphoma Society and NIH DK073098.
IFN‐γ secretion at effector immunological synapses (IS) in vivo
Authors: Lowenstein Pedro R , Barrett Robert , Puntel Mariana , Yang Jieping , Sanderson Nicholas , Bondale Niyati , Kroeger Kurt M , Castro Maria G 
Published: June 2021

In vitro, IFN‐γ secretion is focused towards the immunological synapse (IS), while secretion of TNF‐α is multi‐directional. We have previously demonstrated the polarization of IFN‐ γ within T cells establishing Kupfer‐type or non‐Kupfer type IS with virally infected astrocytes in vivo. We developed a novel adenoviral vector system containing an IFN‐ γreporter to identify IFNγ secretion at immunological synapse in vivo. Astrocytes were infected with this adenovirus, and 30 days later we induced a systemic immune response against Ads, and 14 days after the immunization animals were sacrificed and brains studied by immunohistochemistry and confocal microscopy. Brain sections were stained for TCR, LFA‐1, TK, and IFN‐ γ. Confocal analysis confirmed IFN‐γ polarization, and quantitative analysis was used to demonstrate the expression from the IFNγ ‐reporter adenovirus in astrocytes of immunized mice in contact with CTLs, when compared to non‐immunized mice. These data suggests that IFN‐γ is secreted across the immunological synapse in vivo towards the target virally infected cell.This work was funded by grants from NINDS, NIH.
Effects of Antiretroviral Protease Inhibitors on Live Poxvirus‐mediated Target Antigen Expression
Authors: Yu Qigui , Shikuma Cecilia , Shiramizu Bruce , Yewdell Jonathan W. , Moss Bernaid , Hu Ningjie 
Published: June 2021

Background: Live poxvirus‐based HIV‐1 vaccines have been tested as therapeutic vaccines and live highly attenuated strains of modified vaccinia Ankara (MVA) has been evaluated as an alternative vaccine against smallpox in HIV‐1‐infected individuals receiving antiretroviral therapy (ART). The objective of this study was to determine the affect of ART on poxvirus‐mediated target antigen expression, processing, and presentation. Methods: Using a recombinant EGFP‐expressing VV (EGFP‐VV), we studied the efficiency of virus‐mediated protein expression in primary human monocytes in the presence of HIV‐1 protease inhibitors (PIs). Results: The PI, atazanavir, significantly inhibited EGFP expression in primary human monocytes infected with EGFP‐VV. Further studies demonstrated that atazanavir could block VV‐induced activation of PI3K signaling pathway in monocytes. PI3K was the most critical pathway among four cellular signaling pathways (PI3K, p38 MAKP, JNK, and ERK) examined in antigen expression by VV‐infected cells, as blocking the PI3K pathway with the specific inhibitor LY294002 at 25 μM exhibited 90.1% decrease of EGFP expression compared to non‐inhibitor‐treated control (DMSO).Conclusions: The HIV‐1 protease inhibitor, atazanavir, significantly inhibited EGFP expression in primary human monocytes infected with EGFP‐VV, probably through blockage of PI3K pathway.