bluuebunny/crossref_metadata_2025_split huggingface dataset:
Voluntary exercise as a preventive strategy against aircraft noise induced cardio/cerebrovascular damage
Authors: Kroeller-Schoen Swenja , Kvandova Miroslava , Schmal Isabella , Kalinovic Sanela , Stamm Paul , Frenis Katelyn , Daiber Andreas , Oelze Matthias , Schulz Eberhard , Jansen Thomas , Munzel Thomas 
Published: April 2020

BackgroundSeveral experimental studies found transportation noise to be associated with oxidative stress‐induced vascular damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial nitric oxide synthase, and vascular infiltration with inflammatory cells. Furthermore, we could show that the AMP‐dependent‐Kinase (AMPK) is involved in the signaling processes leading to exercise‐mediated vascular protection. In the present study, we investigated the activation of AMPK during voluntary exercise as a preventive strategy.Methods and ResultsWild type (WT) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A) for 4 days after 6 weeks of voluntary exercise. We could show that 4 days noise exposure lead to a significant endothelial dysfunction accompanied by and significant increase in oxidative stress. The voluntary exercise training for 6 weeks resulted in a marked improvement of noise induced endothelium dysfunction and activation of ROS sources (NADPH oxidases). The beneficial effects of exercise training in the vasculature are accompanied by improvement of cerebral oxidative stress due to NADPH oxidases (NOX‐1, NOX‐2) and cerebral inflammatory responses (VCAM‐1, PAI‐1, COX‐2, MCP‐1). Transportation noise is disrupting gene expression patterns of circadian rhythm but we could show that exercise training is able to reestablish aortic circadian clock gene expression in noise exposed wild type mice.ConclusionWe here present novel data on exercise training as a protective strategy against negative effects of aircraft noise exposure by conferring AMPK activation. Our data suggest that exercise training might be an attractive mitigation strategy to protect the general population from noise‐induced cardiovascular damage. Especially patients at high cardiovascular risk could benefit from supervised exercise training to prevent additive cardio/cerebrovascular damage in response to transportation noise exposure.Support or Funding InformationGerman Research Foundation (Deutsche Forschungsgemeinschaft) DFG
Epinephrine Increases Middle Cerebral Artery Blood Velocity in Response to Progressive Central Hypovolemia in Healthy Humans
Authors: Vo Christina C. , Joyner Michael J. , Curry Timothy B. , Convertino Victor A. , Baker Sarah E. 
Published: April 2020

ObjectivesWe aimed to determine if epinephrine played a beneficial role on middle cerebral artery velocity (MCAv) during physiologically stressful stimuli prior to cardiovascular collapse. MCAv was assessed during lower body negative pressure (LBNP) under conditions of a saline or epinephrine infusion. We hypothesized that (1) epinephrine would augment the change in MCAv from baseline to LBNP tolerance, (2), epinephrine would increase MCAv for a given LBNP stimulus, (3) at a given percent of LBNP tolerance epinephrine and saline will be similar and (4) that epinephrine would improve LBNP tolerance.MethodsNine participants (35±9yrs, n=5 male, 4 female) underwent a LBNP protocol to physiological tolerance during two study visits, performed at least two weeks apart, and randomized to saline or epinephrine (dose=0.1μg/kg/min) infusions (peripherally‐ inserted central catheter). Blood pressure (radial artery catheter) and middle cerebral artery velocity (transcranial Doppler) were assessed. MCAv and cerebrovascular conductance index (CvCi) were analyzed during baseline (three minutes), physiological tolerance (one minute), during LBNP at a given stimulus (three minutes; −15, −30, −45 mmHg of LBNP), and during relative percentages of LBNP tolerance [three minutes; 20, 40, 60, and 80% of LBNP tolerance time (s)]. Baseline was defined as measures taken after 15 minutes of saline or epinephrine infusion.ResultsIn both saline and epinephrine conditions, MCAv and CvCi decreased from baseline to tolerance (Saline MCAv: 69.7±7.5 vs 44.9±4.9 cm/s, p<0.05; Epinephrine MCAv: 80.9±5.9 vs 56.5±6.7 cm/s, p<0.05; Saline CvCi: 0.69±0.06 vs 0.58±0.067 cm/s/mmHg, p>0.05; Epinephrine CvCi: 0.80±0.06 vs 0.70±0.078 cm/s/mmHg, p<0.05). Epinephrine augmented MCAv at a given LBNP stimulus from baseline to −15, −30, and −45 mmHg (MCAv: Treatment effect: p<0.05; CvCi: Treatment effect: p=0.05). At a relative percent of LBNP tolerance, epinephrine increased MCAv, but when blood pressure was controlled for with CvCi there was no treatment effect between epinephrine and saline (MCAv: Treatment effect: p<0.05; CvCi: Treatment effect: p>0.05). Time to tolerance was not significantly different between saline and epinephrine conditions (1469±168 vs. 1445±82s, p=0.88).ConclusionsEpinephrine increased MCAv during LBNP. These data suggest that epinephrine plays a beneficial role during stressful physiological stimuli such as hemorrhage in humans by augmenting cerebral blood flow prior to cardiovascular collapse. However, epinephrine did not improve LBNP tolerance.Support or Funding InformationThe United States Department of Defense W81XWH‐13‐2‐0038
An Innovative Approach For Demonstrating the Lymphatic System in the Gross Anatomy Laboratory
Authors: Lackey-Cornelison Wendy , Bauler Timothy 
Published: April 2020

INTRODUCTIONFrom a gross anatomy perspective, the lymphatic system is difficult for students to observe and comprehend in the laboratory setting. Aside from the thoracic duct and spleen, many lymphatic structures are not often preserved well in embalmed cadavers or are damaged or destroyed during the dissection process. This presentation describes an intervention that was created to enhance gross anatomy learning of the lymphatic system.AIM
To describe a case‐based anatomy laboratory approach that engages students and emphasizes the clinical relevance of gross anatomic knowledge of the lymphatic system.INSTRUCTIONAL METHODGross anatomy at Western Michigan University Homer Stryker MD SOM (WMed) is prosection‐based and taught within an integrated systems‐based curriculum. The laboratory session covering the lymphatic system occurs during the Immunology and Infectious Disease course. Organization of the session uses a combination of guided and cooperative learning techniques.Student anatomy groups (6 students/group) progress through 7 cadaver stations, each having an associated clinical case. The cases encompass a variety of cancers, infections, and traumatic injuries to lymphatic system structures. At each station, students must identify the normal structures involved in the clinical scenario. In addition, students pin on the cadavers the location of lymph node groups that would likely be enlarged and/or need to be biopsied based on patient presentation and diagnoses. Cases also include short‐answer clinical application questions. Students within their groups work independently to identify and pin structures and compose their short answers. During the session, faculty circulate throughout the lab to confirm student answers and provide additional information when necessary.RESULTSPrior to this innovation, student feedback was below average and many students had difficulty seeing the relevance of the laboratory session. Since flipping the approach, evaluations have improved. Student comments expressing frustration over not being able to observe structures decreased. The number of comments expressing confusion about the purpose of the laboratory session and questioning if it is an effective use of time has also been reduced.DISCUSSION AND CONCLUSIONThis approach highlights the importance of the lymphatic system which is often overlooked in the gross anatomy laboratory. It provides faculty with a useful tool to help students see the clinical relevance of lymphatic gross anatomy and how this knowledge is applicable to physical examination and patient evaluation.Support or Funding InformationThere is no external funding for this project.
Identification and functional characterization of a biflavone as a novel inhibitor of TRPV4‐dependent proatherogenic processes in macrophages
Authors: Rahaman Shaik O. , Alharbi Mazen O. , Dutta Bidisha , Goswami Rishov 
Published: April 2020

Atherosclerosis, a chronic inflammatory disease, is the major cause of mortality and morbidity in the United States. Studies suggest that arterial stiffness is a marker and a risk factor for atherosclerosis. Recent reports from our laboratory showed that TRPV4 (transient receptor potential channel of the vanilloid subfamily 4), a mechanosensitive ion channel, plays a role in oxidized LDL (oxLDL)‐induced macrophage foam cell formation, a critical process in atherogenesis. We performed a high‐throughput screening for antagonists of TRPV4 from a library of 2000 natural compounds using a fluorometric imaging plate reader (FLIPR)‐based Ca2+ influx assay. We identified ginkgetin, a biflavone, as a novel small molecule chemical inhibitor of TRPV4. Primary and secondary screening was performed with mouse bone marrow derived macrophages (BMDMs) to assess the ability of ginkgetin and other candidates to inhibit TRPV4‐dependent Ca2+ influx. In our hand’s, ginkgetin demonstrated an IC50 of 0.5 μM for inhibition of TRPV4‐dependent Ca2+ influx. Furthermore, we found that antagonism of TRPV4 by ginkgetin blocks oxLDL‐induced macrophage foam cell formation. Moreover, we found that ginkgetin treatment 1) attenuated oxLDL uptake but not its cell surface binding in BMDMs, 2) inhibited lipopolysaccharide‐induced phosphorylation of JNK, and 3) inhibited oxLDL‐induced expression of proinflammatory cytokines. Taken together, our results show that ginkgetin is a novel inhibitor of TRPV4‐mediated proatherogenic processes in macrophages.Support or Funding InformationThis work was supported by NIH (1R01EB024556‐01) and NSF (CMMI‐1662776) grants to Shaik O. Rahaman.
Identification of toxic metabolites produced by Batrachochytrium dendrobatidis fungus
Authors: Moore Lyndsey E. 
Published: April 2020

Batrachochytrium dendrobatidis, or Bd, is a fungus that causes chytridiomycosis in amphibians, a disease responsible for the rapid decline in amphibian populations globally. The pervasiveness and mortality rates of the Bd fungus has spurred researchers to discover why the fungus is so lethal in various species of frogs, salamanders, and caecilians. While it is known that the fungus affects the skin of amphibians and causes death through suffocation via populating in the pores of adult amphibians, little is known about the active compounds in the fungus. An understanding of the methods of infection will aid in the creation of safe ways to treat amphibians and prevent further outbreaks. To determine the metabolites excreted by the fungus, the culture medium was filtered, dried, and analyzed by LCMS. A Daphnia assay was developed in order to aid bioactivity‐guided fractionation. Preliminary data suggests the presence of several compounds of interest in the dried metabolites. The masses of the peaks of interest were used to guide further isolation and identification of compounds.Support or Funding InformationFunded by a SURF grant from the University of Tampa
A Microfluidics Approach to the High‐Throughput Generation of Quantifiable Cell‐Free Protein Synthesis Systems
Authors: Bashaw Benjamin T. , Peterson Andy T. , Schildknecht Kaitlyn T. , Tauchen Ali T. , Tittor Raechel T. , Gomez Paul , McKlin Sam , Chen Queena , Mazariegos Christopher , Zhou John , Seligmann Haley , Heyer Laurie L. , Campbell Malcolm , Poet Jeffrey L. , Eckdahl Todd T. 
Published: April 2020

Synthetic biologists construct parts, devices and systems to engineer cells for applications in medicine, biofuels, chemical commodities, and the environment. A common problem with projects that focus on the synthesis of natural and engineered proteins is unpredictable translation directed by ribosomal binding sites (RBS). Researchers have hypothesized that base pairing interactions between RBSs and downstream coding sequences form secondary structures that affect the efficiency of translation initiation. Bicistronic designs (BCDs) were developed in 2013 by Drew Endy and his colleagues to enable more predictable and reliable in vivo translation. BCDs have an RBS that leads to the production of a leader polypeptide with no functionality and a second RBS that directs the production of a protein of interest. BCDs are better at producing predictable protein levels in bacterial cells than simple RBSs, thereby improving the ability of BCDs to function reliably and predictably as classic synthetic biology parts. In a companion study, we used GFP expression to compare the translational efficiencies of 19 BCDs during cell‐free protein synthesis (CFPS) to their efficiencies in vivo and found a rank correlation of 0.88. This report describes our efforts to expand the toolkit for CFPS protein production to microfluidic droplets. We used a microfluidic flow control system to rapidly produce nanoliter‐scale droplets and characterized them with microscopy. Image analysis of the droplet fluorescence intensities allowed us to quantify and compare BCD‐directed protein synthesis within droplets. We automated this process for many images to accelerate the workflow. We focused on three BCDs for CFPS of GFP in droplets and documented significant increases in observed fluorescence compared to batch CFPS outside of droplets. We also found that the rank order function for the three BCDs was the same in droplets as it was in batch CFPS. Our results support the use of BCDs to gain predictability of protein production in CFPS. These results set the stage for partitioning large libraries of gene regulatory combinations into microfluidic droplets to find the best combinations suited for a given synthetic biology application.Support or Funding InformationNSF RUI MCB‐1613281 to Missouri Western State University, NSF RUI MCB‐1613203 to Davidson College
A novel method for quantifying the permeability of isolated small venules
Authors: Koller Akos , Deng Wensheng , Szenasi Annamaria , Zhang Bin , Kandhi Sharath , Huang An , Sun Dong 
Published: April 2020

BackgroundThe wall of venules is the primary site for the regulation of the transfer of water, ions and larges molecules in order to maintain tissue homeostasis. The impairment of venular permeability can cause tissue edema, followed by organ dysfunction. To date, although some methods are available to visualize the permeability of vessels, the quantification of the results remains elusive. Thus the aim of the present study was to develop a novel method to quantify the permeability of small isolated venules.MethodsMouse mesenteric venules (160–200 μm diameter at 8.0 mmHg of perfusion pressure) were isolated, cannulated in a vessel chamber and perfused with MOPS‐PSS (pH=7.4 at 37°C). The perfusion chamber contained two glass cannulas (inflow and outflow). A PE tubing of 15 mm in length with a rectangular window (2 × 7 mm) carved in the center is pre‐inserted onto the inflow pipette. After a venule was cannulated, the PE tubing was pushed forward (directed from inflow to the outflow pipette) to create a small sealed pool between the two cannulas (see the illustration). The chamber solution was then aspirated, the micro‐pool was washed and filled with 30 μl fresh MOPS‐PSS through the opened window. The inflow and outflow pressures were set at 8 cmH2O to maintain a constant intravascular pressure. The perfusion apparatus was then placed into a 37°C humidified incubator to equilibrate for 30 minutes. After equilibration, a one‐cmH2O pressure gradient was established by an increasing the inflow pressure and a decreasing the outflow pressure equally to create a constant intraluminal flow composed of MOPS‐PSS containing 5×10−4 M Evans blue dye (EBD). Thus, changes in permeability of venules could be assessed by determining the EBD in the pool solution using fluorescence (620/680 nm) spectrometry method. The final level of EBD in samples was determined using an EBD standard curve (0.08–20 μg/ml) and normalized to the internal surface area of venules.ResultsHistamine (2×10−5, 2×10−4 and 2×10−3 M) elicited a dose‐dependent increase in EBD permeability from 7.63 ± 0.79 to 21.70 ± 2.28 ng/mm2/min. The histamine‐induced release of EBD was continuous and reached a peak within 15 min, responses that were significantly reduced by triprolidine hydrochloride an H1 receptor inhibitor to 14.71± 2.07 ng/mm2/min. In addition, we have found that 5% erythrocytes lysate (ECL) and 2 μg/ml lipopolysaccharide (LPS) significantly enhanced EBD permeability.ConclusionsUsing this novel micro‐chamber technique, we were able to quantify histamine, ECL, and LPS‐induced increases in permeability of isolated venules, thus this method offers a valuable tool for pharmacokinetic research of permeability at the scale of microcirculation.Support or Funding InformationSupportNIH HL070653 (An Huang) and HL129797 (Dong Sun),Scientific Excellence Program 2019, at the University of Physical Education, Innovation and Technology Ministry, Hungary TUDFO/51757/2019‐ITM (Akos Koller).
Venom peptides as selective inhibitors of bacterial ATP synthase
Authors: Ahmad Zulfiqar 
Published: April 2020

BackgroundIt is predicted that by the year 2050 world will face 10 million additional deaths per year due to antibiotic resistance. Misuse and overuse of antibiotics, is making microbes resistant to normally effective antibiotics. Therefore, it is of necessary to find different ways to combat microbial infections. ATP synthase is the main source of cellular energy production in almost all organisms from bacteria to men. Selective inhibition of bacterial ATP synthase to kill bacteria provides an effective way to eradicate antibiotic resistant bacteria. Venom peptides from many sources bind and inhibit ATP synthase. Venom peptides bind at the βDELSEED‐motif of ATP synthase. Although βDELSEED‐motif is highly conserved throughout the evolution but is skirted by more than twenty variable amino acids. We are identifying and characterizing the selective venom peptide inhibitors of ATP synthase using Escherichia coli as a model organism.MethodWild type, null, and mutant E. coli strains are used to select the strong venom peptide inhibitors of ATP synthase. Growth of E. coli strains is measured on fermentable and non‐fermentable carbon sources in presence and absence of venom peptides. F1Fo ATP synthase is isolated by harvesting cells in the minimal media, lysing cells by French Press, and isolating membrane bound ATP synthase by multiple high‐speed ultracentrifugation. A variety of venom peptides are used to inhibit ATP synthase. Inhibitory potency of venom peptides is augmented by incremental addition of charge and α helicity.ResultsVenom peptides cause variable degree of ATP synthase inhibition. Modifications of venom peptides cause increased inhibition. Addition of a c‐terminal NH2 group in venom peptides augment the inhibitory effects by about 100‐fold. Venom peptides also show synergistic inhibitory effects on ATP synthase.ConclusionsVenom peptides potently kill E. coli cells by binding at βDELSEED‐motif of ATP synthase. ATP synthase can be used as a potent molecular drug target to combat antibiotic resistant bacterial infections.Support or Funding InformationWarner/Fermaturo and ATSU Board of Trustees Research Grant
Stress Promotes a More Invasive Phenotype in Human Melanoma Cells
Authors: Amomoy Jerry , Barkoudeh Laila , Phung Vanessa , Nguyen Cecilia , Fajardo Abigail , Zarghooni Melody , Rosero Rebecca , Klettke Elizabeth , Villares Gabriel J. 
Published: April 2020

Growing evidence suggests that stress plays a vital role in metastasis and tumor development by activating the sympathetic nervous system. The catecholamines released into the tumor microenvironment (TME), specifically norepinephrine (NE), results in a cascade effect leading to a variety of pro‐metastatic activities that sustain tumor growth and increase melanoma aggressiveness. Most notable are the secretion of cytokines and the stimulation of tumor‐associated macrophages (TAMs). Using a co‐culture system of melanoma cancer cells and macrophages we found that sustained exposure of NE in the microenvironment induced the release of tumor‐growth and progression‐associated cytokines from TAMs. Of the upregulated cytokines found; IL‐11, IL‐24, GRO‐a, DKK‐1, and angiopoietin‐2 are known to induce growth, migration, invasion, and tumor development in human melanoma. Our next steps include validating the cytokine array using real time PCR and using an ELISA assay to quantify protein levels of antigens associated with the cytokines secreted from the cells and macrophages.Support or Funding InformationUS Department of Education for the HSI‐STEM Grant University of St. Thomas for Student Research for partial funding
Using Interactive Technology in an Integrated Human Physiology and Functional Anatomy Course to Enhance Student Engagement, Knowledge, and Retention
Authors: Stokes Jennifer Ann , Silverthorn Dee 
Published: April 2020

The curriculum for a traditional two‐semester anatomy and physiology (A&P) course was revised into an integrated two‐semester physiology and functional anatomy course for undergraduate students going into the health professions. The revised curriculum implemented the use of digital learning technology with the cloud‐based ADInstruments (ADI) Lt learning platform. This platform provides students in the classroom and laboratory with interactive and immersive experiences aimed at enhancing knowledge retention and practical application. Students enrolled in the first semester (fall 2019) of the two‐semester course sequence completed individual lessons and group lab activities throughout the semester using ADI‐supplied Lt lessons with instructor modifications. The goals of the individual lessons were to provide students with opportunities to review the difficult course concepts, allowing additional exposure to the content in a new format, and opportunities to practice applying the content to clinical scenarios. Students received immediate feedback on their answers as part of the lesson. The goals of the group lab activities were to provide the students with the opportunity to apply course knowledge to a real‐life physiological scenario, formulate a hypothesis, record and analyze data, and draw conclusions. Group lab activities included analysis of heart rate, muscle contraction and EMG, grip strength and fatigue, and a guided heart dissection. Student surveys assessed student perceptions and engagement with the ADI Lt system. Summative assessments of student knowledge and retention included unit exams, a cumulative final exam, and lab practical exams. Summative assessment data were compared to previous course cohorts. Data collection followed guidelines approved by the Centenary College Institutional Review Board (Protocol #18‐002).Support or Funding InformationThis project is supported by the Teaching Career Enhancement Award from The American Physiological Society.