bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise Improved Cognitive Impairment in Aging Mice via Skeletal Irisin
Authors: Behera Jyotirmaya , Ison Jessica , Tyagi Neetu 
Published: April 2020

The progressive decline of neurological learning and memory is rising as the lifespan increases in humans. The mechanistic basis of aging‐associated memory impairment is not still clearly understood. It is also currently unknown whether irisin is secreted by bone tissue after exercise or whether it regulates brain memory function via distant paracrine signaling in vivo. Here we show that age‐related suppression of irisin expression is linked with skeletal bone loss and memory disturbances in the aging brain. However, daily treadmill exercise (Ex) was found to restore the bone and memory loss in the aging mouse. To test the hypothesis, we employed young and aged male/female C57BJ/L6 wild‐type (WT), which were grouped as follows: Young (Yg, 3month);(ii) Yg+Ex(iii) Aged(Ag.18–22 month old); (iv) Ag+Ex. The selected mice were exercised for this 12‐week duration on a treadmill, with controlled speeds of 7 meters/min for the first week, 9 meters/min for the second week and 11 meters/min the following weeks for a total of 330 meters every day. The results show that treadmill exercise‐induced high levels of irisin mRNA transcript as well as protein expression in murine femoral bone tissues. This resulted in increased trabecular and cortical bone formation in aging mice (AG+EX) in vivo. On the other hand, AG+EX mice displayed an increased plasma and hippocampal level of bone‐derived Irisin (FNDC5). Interestingly, AG+EX mice showed higher behavioral proficiency and more robust long‐term and short‐term memory compared to AG mice. The mechanistic study shows that AG+EX mice display an increased irsin dependent upregulation of neuronal derived neurotropic factor (NDNF) in mouse hippocampus probably via epigenetic inhibition of H3K27me3 methylation at the promoter. Hippocampal overexpression of irisin by Lentiviral FNDC5/irisin administration rescues age‐memory impairment, whereas blockade of brain irisin attenuates the neuroprotective actions of physical exercise on memory in AG mice. Taken together, our findings suggest that physical exercise increases irisin production in bone and that an increase in paracrine irisin signaling in the brain enhances memory function in aging mice.Support or Funding InformationAcknowledgmentFinancial support from National Institute of Health grant AR‐067667‐NT is greatly acknowledged.
PMSF, SFN, and Metformin Reduce Alpha‐synuclein Aggregation in a Yeast Model of Parkinson’s Disease
Authors: Kozub Noah Joseph , Van Brysgel Taylor , Yerxa Christopher Anthony , Moss Stephen , Haak Victoria Melina , Austriaco Nicanor 
Published: April 2020

Parkinson’s Disease (PD) is the second most common neurodegenerative disease in humans. PD is marked by Lewy body formation in the brain, which disturbs the dopamine transfer system across neurons. Previous studies have shown that the protein, α‐synuclein, is a major contributor in the formation of Lewy bodies. In this study, we modeled α‐synuclein aggregation in the budding yeast, Saccharomyces cerevisiae. Using this model, we treated cells, in separate trials, with phenylmethylsulfonyl fluoride (PMSF), sulforaphane (SFN), metformin, and methylene blue (MB). Our data suggests that a 4mM concentration of PMSF, 200μg/ml of SFN, and 50mM of metformin significantly reduce protein aggregation. Different concentrations of MB had no effect on α‐synuclein aggregation.Support or Funding InformationOur laboratory is supported by NIH Grant NIGMS R15 GM110578 awarded to N. Austriaco and P20GM103430 awarded to the RI ‐ INBRE Program for SURF training
Simple and Rapid Slide‐based Mass Spectrometry Workflows Applied to N‐glycan Analysis of Cells, Biofluids and Antibody Arrays
Authors: Drake Richard R. , Black Alyson P. , Blaschke Calvin , Mehta Anand S. , Angel Peggi M. 
Published: April 2020

Alterations in glycosylation have long been associated with the development and progression of many types of chronic and acute diseases. Despite major advances in technology for analysis of the glycome, there remain barriers to both non‐glycomic and glycomic researchers for implementing large scale glycan analysis workflows applied to biofluids and cells. Most current liquid chromatography and mass spectrometry workflows require extensive sample purification and processing prior to analysis, expensive reagents and significant technical expertise. Our group has recently adapted tissue‐based mass spectrometry imaging methods to develop streamlined and simplified approaches to efficiently profile N‐glycan constituents in biofluids and cultured cells. A recombinant PNGaseF Prime enzyme is sprayed on to glass slides containing the biological sample of interest, followed by digestion, coating with chemical matrix and analysis of released N‐glycans by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). This is accomplished with a solvent sprayer, and the reactions are essentially a solid‐phase format with minimal solvent or sample diffusion. One application example is an antibody slide array approach to directly profile N‐glycans of captured serum glycoproteins like immunoglobulin G. This method requires only a few microliters of sample, rapid processing workflows that require no purification or sugar modifications prior to analysis, and the data readout can be configured as a bar‐code format. Multiplexed slides arrays with seven serum glycoprotein‐targeted antibodies are currently in evaluation, and there is no limit to how many antibodies could be included. Another application is for the N‐glycan analysis of cultures cells on glass slides. Our current method using 8‐well chamber slides is rapid and can be done within 4 hours of completing cell culture, requires as few as 3000 cells per replicate and can include stable isotopic labeling of N‐glycans. The method is amenable to any experimental application that uses cultured cells, can be easily inserted into conventional cell function studies, and depending on the cell type, can generate single cell glycomic information. Both the antibody and cell culture approaches are being adapted to the analysis of immune cell isolates, as well as direct profiling of biofluids like serum and urine. The long‐term goals of these approaches are to provide validated workflows such that any research or core laboratory with a MALDI mass spectrometer will be able to perform routine N‐glycan analysis on the most common types of samples.Support or Funding InformationU01CA242096 NIH Common Fund in Glycoscience
Saccharomyces cerevisiae Cell Wall Isolates are Potential Inhibitors of Bacterial Growth
Authors: Gudell Evan Victor Judd , Callahan Kevin 
Published: April 2020

Saccharomyces cerevisiae cell wall components are thought to bind and help pass pathogenic bacteria, such as E. coli, through the intestines
1. The binding between bacteria and S. cerevisiae is thought to occur between type‐1 mannose specific fimbriae, a common feature of pathogenic bacteria, and the mannoproteins that comprise 30–50% of the cell wall of S. cerevisiae by weight
2,
3,
4. With the fimbriae bound to mannoproteins, bacteria are unable to adhere to the walls of the intestine and thus, no colonization occurs. This interaction provides a potential antibiotic free method to prevent E. coli infection. The goals of this project are two‐fold. First, to develop a cell wall harvesting procedure and characterize the cell wall fractions. Second, to evaluate the binding interaction of S. cerevisiae with E. coli and its effect on E. coli proliferation. A cell wall isolation procedure has been optimized using temperature induced autolysis of a cell culture at 50 °C and pH 5.0 for 24 hours followed by purification washes with salt solutions. Cell wall fractions have been characterized using the Bradford assay, Coomassie stained SDS gels, and Western blot analysis employing the lectin Concanavalin A antibody to detect mannose. The cell wall fractions have been found to contain high levels of mannoproteins. An in‐vitro binding assay, adapted from Ganner et al. 2013, has been employed to evaluate the interaction between the cell wall fractions and E. coli. Cell wall coated microplate wells display a faster progression to log phase than controls due to the cell wall‐fimbriae binding interaction increasing retention of initial colony forming units. In‐vivo, a stronger binding interaction would inhibit bacterial infection by disrupting initial attachment of E. coli to the intestinal lining. Work is currently being performed to better understand factors influencing the binding mechanism as previous studies have indicated an unclear connection between total mannoprotein content and binding capacity.
2Support or Funding InformationSJFC Internal funds
Apoptosis in Neuronal Populations of C. Elegans through Exposure to Caffeine
Authors: Leeman Jacob T. , Fong Ethan , Madejski Sophia , Iyer Ananya , De Luke 
Published: April 2020

Caffeine is the most widely used psychoactive drug in the world and forms a mild dependency in individuals who overuse the drug for an extended period. Other stimulant drugs, including methamphetamines, have been shown to induce apoptosis in the brain’s reward pathways, suggesting that stimulants may lead to apoptosis to lasting neuronal damage. Caffeine has been shown to induce apoptosis in gastric cancer cells in vitro as well as neonatal rat brain and cortical cell cultures. In C. elegans, the homolog of the p‐53 pathway is the CEP‐1 pathway. Caffeine induces apoptosis in human osteoblasts via the p53, Bax, and caspase 3 pathways. However, other studies suggest that caffeine produces inverse effects; caffeine exposure has been reported to increase longevity of Caenorhabditis elegans through activation of the IGF‐1 signaling pathway. Our current data clarifies the relationship between caffeine exposure and CEP‐1 via TG‐12, a C. elegans strain with CEP‐1:: GFP fusion gene.Here we discuss the results of caffeine exposure on TG‐12 worms. Early data indicates that exposure to high levels of caffeine leads to apoptosis in the nerve ring region of the worm. Here we attempt to identify the affected neuronal populations. We plan to further investigate the relationship between CEP‐1 and caffeine exposure in a dose‐dependent fashion via qRT‐PCR.Support or Funding InformationThis work was supported and funded by the Nueva School. The Shen Lab at Stanford University provided lab equipment and OH11061 worms. Worms and technical support were provided by Caenorhabditis Genetics Center (CGC) ‐ College of Biological Sciences
Oral Contraceptives Do Not Alter Sympathetic Neural Control of Blood Pressure in Young, Healthy Women
Authors: Pletsch Michaela C. , Limberg Jacqueline K. , Cupeiro Rocío , van Helmond Noud , Harvey Ronée E. , Joyner Michael J. , Curry Timothy B. , Baker Sarah E. 
Published: April 2020

BackgroundSympathetic nerve activity and its effect on blood pressure are altered by female sex hormones; however, this effect differs between exogenous and endogenous hormones. With oral contraceptive (OC) use, cross‐sectional data has demonstrated higher blood pressure (BP) with no corresponding change in muscle sympathetic nerve activity (MSNA). This results in a higher BP/MSNA ratio with OC use although contributing mechanisms are unclear. The higher BP/MSNA ratio in women on OC suggests OC use may limit the ability of sympathetic baroreflex (sBRS) to suppress MSNA. Alternatively, a “burst” of MSNA could result in a greater change in BP (augmented neurovascular transduction).ObjectiveThe goal of this study was to determine if OCs alter blood pressure control through autonomic mechanisms in young women.HypothesesWe hypothesized (1) sympathetic baroreflex sensitivity would be decreased and (2) neurovascular transduction would be augmented in women on OCs compared to naturally cycling women.MethodsWe conducted a retrospective analysis of data from healthy young women taking OCs (n=30, 25±4yrs) and with natural menstrual cycles (n=23, 27±4yrs). Women were studied during the placebo phase of OC use or early follicular phase of the menstrual cycle. Heart rate (HR, 3‐lead ECG), BP (arterial line or photoplethysmography for both groups), and MSNA (peroneal nerve microneurography) were measured over 5 min of quiet rest and data were analyzed for measures of sBRS and neurovascular transduction (Ensemble, Elucimed Inc., Dunedin, New Zealand).ResultsGroups did not differ in mean BP (Control: 94±9, OC:92±8mmHg, p=0.60), or HR (Control: 61±8, OC: 62±9 bpm, p=0.57), but women on OCs had lower MSNA than controls (Control: 16±6, OC: 12±5 bursts/min, p=0.006). There were no significant differences in TPR (Control: 0.022±0.005, OC: 0.020±0.005 mmHg min/L, p=0.12), however there was a trend toward increased cardiac output in women on OCs (Control: 4.45±0.86, OC: 4.94±1.02 L/min, p=.068). There were no significant group differences in sBRS (Control: −4.3±2.1, OC: −4.0±2.6 bursts ·100 heartbeats−1 ·mmHg−1, p=0.79), or neurovascular transduction (Control: 0.093±0.042, OC: 0.091±0.058 ΔmmHg/% burst area, p=0.87). Furthermore, there were no significant correlations between BP and BRS, MSNA, or transduction in either group.ConclusionsOur data strengthen previous findings which have shown women taking OCs have higher BP for a given MSNA. The analysis we performed build on these results and demonstrate that the increase in BP for a given MSNA in women taking OCs is not due to attenuated sBRS or augmented neurovascular transduction. This work has advanced our understanding of the alteration of blood pressure with OC use in young women.Support or Funding InformationNIH HL083947
‘SPARC:The Structure of Vagal Nociceptive Nerve Fibers in the Mouse Esophagus’
Authors: Patil Mayur J. , Harsanyiova Jana , Kim Seol-Hee , Taylor-Clark Thomas E. , Kollarik Marian 
Published: April 2020

The vagus nerves provide afferent nerve fibers with nociceptive sensory properties to the esophagus. However, it is unknown which esophageal layers are innervated by these vagal nociceptive fibers. We hypothesized that the vagal nociceptive TRPV1‐positive afferent fibers innervate esophageal mucosa. We evaluated our hypothesis by using genetic neuronal tracing in several mutant mice, including two new strains we generated. The wholemount preparations of separated esophageal mucosa and muscle were immunostained for appropriate fluorescent proteins and imaged by spinning‐disk confocal microscopy. In the TRPV1‐Flp/RC: FLTG mice(N=8) in which TRPV1‐expressing cells express tdTomato the TRPV1+ fibers with varicose appearance densely innervated both the mucosa and the muscle. In the mucosa the TRPV1+ fibers are located just beneath the epithelium, run in parallel registers of two or more fibers, have craniocaudal orientation and branch repeatedly. In the muscle the TRPV1+ fibers form a dense network in the myenteric plexus innervating virtually all myenteric ganglia forming intraganglionic varicose endings (IGVEs). Many TRPV1+ fibers connecting IGVEs run in parallel to the fibers of outer and inner striated muscle. In the TRPV1‐Flp/Tac1‐Cre/RC:FLTG mice(N=4) in which GFP is selectively expressed in cells positive for both TRPV1 and Tac1 (the marker of esophageal nociceptors derived from neural crest) the esophageal innervation by TRPV1+/Tac1+ fibers mimicked the dense innervation by TRPV1+ fibers. In contrast, in the TRPV1‐Flp/P2X2‐Cre/RC:FLTG mice(N=4) in which GFP is selectively expressed in cells positive for both TRPV1 and P2X2 (the marker of esophageal nociceptors derived from placodes) the TRPV1+/P2X2+ fibers were almost absent in the esophagus. Consistent with this finding, in the P2X2‐Cre mice unilaterally injected with AAV9‐FLEX‐EGFP virus into vagal ganglia(N=2) in which GFP is selectively expressed in vagal P2X2‐positive fibers, the nodose TRPV1‐negative tension mechanosensor nerve terminals (intragangionic laminar endings) were visualized in the esophageal muscle. Finally, in the TRPV1‐Cre mice unilaterally injected with AAV9‐FLEX‐EGFP virus into vagal ganglia(N=3), in which only the vagal TRPV1‐positive fibers express GFP, the vagal TRPV1+ fibers had the same pattern as TRPV1+/Tac1+ fibers, but with lower density and patchy distribution. Our data indicate that vagal nociceptive TRPV1+ fibers innervate both the esophageal mucosa and myenteric ganglia and originate from neural crest‐derived jugular portion of the vagal jugular‐nodose ganglia complex.Support or Funding InformationNIH SPARC
Transcriptome analysis of Rrp6p’s role in intron retention during the stationary phase of Saccharomyces cerevisiae
Authors: Villalta Oscar , Callahan Kevin , Myres Jacquelyn , Ashton John 
Published: April 2020

Introns are non‐coding RNAs that are readily degraded into single nucleotides within the nucleus where they can be recycled in another transcription cycle. Unspliced introns form 3‐D structures at their 5′ end, never separate from their splicing factors and are stable during and after pre‐mRNA modifications
(4). Recently it was observed that retention of introns in Saccharomyces cerevisiae increases when the cells are in a nutrient deficient environment, specifically stationary phase
(3,
4,
5). Transcriptomic and genetic analyses showed that intron retention promotes resistance to starvation by downregulating ribosomal protein genes downstream of nutrient‐sensing TORC1 and PKA pathways
(3). Yeast cells that cannot synthesize introns or have a low concentration of them fail to survive in stationary phase, suggesting that introns are necessary for the survival of the organism during starvation. Rrp6p is a 3′→5′ RNA exonuclease that associates with the nuclear exosome
(1). This complex participates in 3′ end formation and degradation of a variety of non‐coding RNAs and unstable transcripts
(1,
2). We hypothesized that yeast cells lacking Rrp6p will retain more introns than a wild type strain, thus transcriptome analysis of this strain during starvation conditions will lead to a better understanding of intron retention. We monitored the growth of WT and rrp6‐Δ strains during prolonged stationary phase and the subsequent lag, log phases following placement into fresh media. This analysis identified the time frame at which each strain exited stationary phase and entered log phase. We collected RNA from each strain during stationary phase and early log phase and performed transcriptome analysis. Data analysis was performed using the scripting program, R, to identify introns whose expression significantly changes. Introns identified from this analysis will be confirmed using quantitative PCR.Support or Funding InformationSJFC internal funds
Evaluation of Pulse Arrival Time Model to Estimate Systolic Blood Pressure during Exercise
Authors: Hedge Eric T. , Amelard Robert , Hughson Richard L. 
Published: April 2020

Pulse arrival time (PAT) is a method used to estimate systolic blood pressure (SBP), as the amount of time it takes for a pulse to travel from the heart to a peripheral location is inversely related to blood pressure. However, the validity and accuracy of this method’s blood pressure estimation has been questioned. Therefore, the purpose of this study was to evaluate the accuracy of a PAT model’s estimation of SBP over a range of exercise intensities. Six participants (5 men, 1 woman; age: 26 ± 4 yrs) completed three cycling exercise tests (25 Watt/min ramp incremental test, and moderate and heavy pseudorandom binary sequence exercise) during three separate laboratory visits. PAT was calculated as the time difference between the R‐wave of an electrocardiogram and the pulse arrival at the forehead measured with a pulse oximeter. SBP was estimated using the following equation: SBPPAT = 64.578/(PAT) – 43.957, and was compared to calibrated brachial blood pressure measured at the finger (FBP) by photoplethysmography during the exercise trials. Participant blood pressure responses were pooled, and Bland‐Altman analysis was conducted to evaluate the accuracy of estimated SBP for each exercise test. PAT model estimation of SBP had the smallest bias during heavy (−2.8 mmHg), then moderate (8.1 mmHg), and the largest bias during ramp incremental exercise (−11 mmHg), with their limits of agreement being between −56 and 50 mmHg, −29 and 45 mmHg, and −74 and 53 mmHg, respectively. Linear regression of the ramp incremental SBP response revealed that SBP estimated from the PAT does not increase by the same magnitude as the pressure measured at the finger (SBPPAT = 0.295 · SBPFBP + 106.236, r2 = 0.350, p < 0.05). Overall, these findings support that SBP estimated by PAT is linearly related to brachial SBP measured at the finger; however, this PAT model is a poor estimator of absolute SBP during exercise ranging from moderate to maximal intensities.Support or Funding InformationSupported by NSERC.
Mammalian Target of Rapamycin Mediates Expression and Activity of ADAM 17 in Diabetic Kidney Disease
Authors: Abraham Sachin , Ford Bridget Marie 
Published: April 2020

Diabetic kidney disease is a serious complication faced by type 1 and type 2 diabetic patients alike. Albuminuria and extracellular matrix accumulation are prominent features of the disease and this accumulation of extracellular matrix is a contributing factor to renal fibrosis and decline in renal function. The mechanisms involved in the pathogenesis of diabetic kidney disease have not been completely identified.Previous data have illustrated a role for the matrix metalloprotease A Disintegrin And Metalloprotease 17 (ADAM17), known to cleave growth factors and cytokines, in renal cell injury in diabetes. The goal of this study was to identify upstream regulators of ADAM17 in the cascade of events contributing to extracellular matrix accumulation in diabetic nephropathy. Using the mTOR complex 1 inhibitor rapamycin, it was determined that increased ADAM17 enzymatic activity and ADAM17 protein expression is dependent on mTORC1 in streptozotocin‐induced type 1 diabetic rats. Inhibition of mTORC1 with rapamycin abrogated the increase in collagen IV α 2 protein expression observed in diabetic rat cortex. Additionally, this study is the first to provide evidence that mTOR complex 1 activates ADAM17 contributing to extracellular matrix accumulation in diabetic nephropathy.Support or Funding InformationThis project was funded by the University of the Incarnate Word, Office of Research and Graduate Studies