bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia/motor neuron interactions in response to ATP and BDNF
Authors: Watters Jyoti J , Mitchell Gordon S , Richards Victoria E 
Published: June 2021

Microglia are CNS resident immune cells that remove cellular debris during normal brain development and synaptic remodeling. Their ability to sense and respond to neuronal signals is critical for maintaining a healthy CNS. Microglial activities are also important in disease, including motor neuron diseases such as ALS as well as spinal injury. However, interactions between microglia and motor neurons are not well understood. Two regulators of microglial and motor neuron function are ATP and BDNF; BDNF plays a central role in neuroplasticity, and ATP potently regulates microglial immune functions. We hypothesized that cell/cell interactions between microglia and motor neurons modulate their respective responses to BDNF and ATP. To test this hypothesis, a transwell system was used wherein motor neuron‐like NSC‐34 cells and N9 microglia were cultured alone or together in transwells without physical contact. BDNF and ATP synergistically promoted ERK activation within 2 hrs in microglia (not motor neurons) in the transwells, but not when cultured alone. ATP also increased TrkB receptor expression in both cell types 24 hrs following exposure, but only when cultured in transwells. Although the soluble molecule(s) mediating this communication are not yet clear, cell/cell interactions appear to be important for amplifying cellular responses to ATP and BDNF.Supported by NIH NS040933 and T32 HL007654 (VER).
Effect of combined nitric oxide and prostaglandin inhibition on hypoxic exercise hyperemia
Authors: Crecelius Anne R , Voyles Wyatt F , Dumke Breanna R , Davis Julia A , Kirby Brett S , Dinenno Frank A 
Published: June 2021

We tested the hypothesis that endothelium‐derived nitric oxide (NO) and prostaglandins (PGs) contribute to the augmented muscle blood flow in hypoxic exercise relative to normoxia. In 8 healthy adults, we measured forearm blood flow (FBF; Doppler ultrasound) during 5 minutes of rhythmic handgrip exercise at 20% maximal voluntary contraction in normoxia (NormEx) and isocapnic hypoxia (HypEx; O2 saturation ~85%). All trials were performed after α‐ and β‐adrenergic blockade (via brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone. FBF responses were determined under control conditions and during combined NO synthase (L‐NMMA) and cyclooxygenase inhibition (ketorolac). Prior to inhibition, steady‐state FBF was significantly augmented during HypEx compared to NormEx (348±28 vs 306±20 ml/min; P<0.05). After inhibition, FBF during NormEx was similar to that observed prior to blockade (290±18; P = 0.11). In contrast, FBF during HypEx was significantly reduced after inhibition (315±24; P<0.05 vs pre), and this was no longer greater than the hyperemic response observed during control NormEx (P = 0.12). We conclude that under sympathoadrenal blockade, NO and PGs contribute modestly to NormEx hyperemia, whereas these locally‐derived substances appear to play a significant role in the augmented hyperemic response observed during HypEx.Supported by HL‐087952
Cholinergic protection against apoptosis in primary cardiac cells
Authors: Li Yi‐Fan , LaCroix Carly , Bergstrom Tyler , Freeling Jessica 
Published: June 2021

The autonomic imbalance, characterized as the elevated sympathetic activity and the suppressed parasympathetic activity, is commonly present in a variety of cardiovascular diseases. However, the functional role of the parasympathetic suppression in cardiac pathology has not been well addressed. Our recent in vivo studies revealed that treatments with cholinergic reagents protected against cardiac dysfunction, while deficiency of M2 receptors increased cardiac susceptibility to stress. In this study, we further observed the cholinergic protection in primary cardiac cells. Pretreatments with cholinergic reagents reduced cell death induced by H2O2 and serum withdrawal. Furthermore, cholinergic treatments attenuated activity of caspase3/7, a central apoptotic signaling pathway. This cholinergic protection against cell death was associated with an enhanced ERK activation. These results suggest that the cholinergic direct effect against cell death may be one of the mechanisms of parasympathetic cardiac protection in cardiac diseases.This study was supported by American Heart Association Grant No. 0835256N, NIH COBRE grant No. 5 P20 RR017662, and INBRE Grant No. 2 P20 RR016479
Increased urothelial ATP release from a subset of OAB patients
Authors: Contreras‐Sanz Alberto , Janska S , Alexander SLH , Lunawat R , Bishara S , Khasriya R , Taylor KMG , Malone‐Lee J , Wildman SSP 
Published: June 2021

Overactive bladder (OAB) is characterised by frequency, urgency and urge incontinence in the absence of infection. We have identified previously unrecognised pyuria in patients diagnosed as having OAB; associated with more severe symptoms.1 Antibiotic treatment of these patients is successful if maintained for long periods. Others have shown that bacteria can thrive in urothelium, resisting host immunity and antibiotics. It is also documented that inflammation, when caused by infection, is associated with increased ATP release from cells, and extracellular ATP signalling is involved in bladder sensation.We hypothesise that in OAB, with pyuria, there is enhanced ATP release from urothelium caused by intracellular bacteria, which ultimately results in increased sensory nerve excitation and heightened symptoms of OAB. Here we begin to investigate our hypothesis.Human bladder urothelium biopsies were obtained using cystoscopy. ATP release from urothelium was measured using a luciferin luciferase assay.Basal and stretch‐evoked (using a hypotonic solution) ATP release was significantly greater from the urothelium of pyuric OAB patients than from non‐pyuric OAB or asymptomatic patients.In summary, this data supports our hypothesis.1. Malone‐Lee et al, Urinary white cells and symptoms of the Overactive bladder. Urodyn. Supplement for International Continence Society (Rotterdam, 2007) Abstract 42.
Differential role of α1‐adrenergic receptor subtypes in Ca2+‐dependent and Ca2+‐independent contraction in developing cerebral arteries
Authors: Mittal Ashwani , Goyal Ravi , Wedhas Nia , Shi Lijun , Longo Lawrence D. 
Published: June 2021

ObjectiveCerebral arteries in the fetus differ functionally from adult. We tested the hypothesis that developmental differences are a consequence of differential activities of α1‐adrenergic receptor (α1‐AR) subtypes.MethodsIn middle cerebral arteries from fetal and adult sheep, we measured responses of Ins(1,4,5)P3, vascular tension, and [Ca2+]i to the α1‐AR agonist phenylephrine (PHE, 10−5 M), in presence of blockers.ResultsIn fetal cerebral arteries, expression levels of each α1‐AR subtype was only ~20% that of adult. In fetus, each subtype specific blocker, 5‐MU (α1A), CEC (α1B) and BMY‐7378 (α1D) inhibited to a degree greater degree PHE‐induced tension and [Ca2+]i, compared to adult. Although in arteries of both age groups, 5‐MU and CEC reduced Ins(1,4,5)P3 responses to PHE ~35%, BMY‐7378 showed no significant decrease in Ins(1,4,5)P3 responses. Also in fetal arteries, the PHE‐induced increase in activated ERKs was blocked by CEC and BMY‐7378, but not by 5‐MU or WB‐4101.ConclusionsIn both age groups α1A‐ and α1B‐AR appear to mediate α1‐adrenergic‐Ins(1,4,5)P3 responses. In the fetus in contrast, α1D‐AR appear to activate the MAPK/ERK1/2 cascade by non‐Ins(1,4,5)P3‐dependent mechanisms. In the immature organism, relative deficiency of specific α1‐AR subtypes, and their differing signaling pathways, may be critical factors associated with dysregulation of cerebral blood flow. (USPHS HD 03708)
Decreases in Cerebral Blood Flow When Upright Are Related to Vestibular Function Regardless of Age
Authors: Serrador Jorge M , Lipsitz Lewis , Black F. Owen , Wood Scott J 
Published: June 2021

IntroductionDecreases in cerebral blood flow occur when moving from the supine to upright posture, yet the cause remains unclear. We hypothesized that impaired vestibular function would produce greater drops in cerebral blood flow in the upright posture.Methods155 subjects were screened for otolith function and based on ocular counter‐roll (OCR), 21 were classified as either young low (YL), young high (YH), old low (OL) or old high (OH). Mean OCR ‐ YL & OL ‐ 0.08±0.05; YH & OH 0.22±0.05. Age for young 33±12, old 69±6 years. Subjects underwent two 30‐min tilt tests on separate days. Cerebral flow velocity (CFV), by TCD, blood pressure (Finapres) and end‐tidal CO2 were measured continuously.ResultsReduced otolith function was associated with significantly greater drops in CFV at all ages (YL: ‐20±4%; OL: ‐22±3%) as compared to normal function (YH: ‐8±2%; OH: ‐13±2%), despite the fact that blood pressure changes were similar in all groups. The reduced OCR groups also demonstrated greater postural hypocapnia (YL: ‐3±1mmHg; OL: ‐4±1mmHg) vs (YH: ‐1±1mmHg; OH: ‐2±1mmHg), however this hypocapnia could only explain ~9‐12% of the 20‐22% decrease in CFV..DiscussionThese data demonstrate that otherwise healthy subjects of all ages with impaired vestibular function demonstrate greater decreases in cerebral blood flow when upright. Thus, vestibular function may play an important role in cerebral orthostatic response.
Neutrophil activation during reperfusion after ischemic stroke in mice
Authors: Morrison Helena Willington , Davis‐Gorman Grace , Frye Jennifer , McDonagh Paul , Funk Janet , Ritter Leslie 
Published: June 2021

Experimental evidence in non‐murine models suggests that activated neutrophils play a pivotal role in cerebral reperfusion injury. Neutrophils release toxic mediators as they initially adhere to the microcirculation and migrate out of the circulation into to brain tissue. In this study we investigated whether systemic neutrophils are activated in mice during the first minutes and 24 hours after reperfusion following ischemic stroke. The filament method of middle cerebral artery occlusion (60 min) and reperfusion (MCAOR) was performed in male C57Bl/6J mice (22‐25g). Blood was drawn from the aorta after 15 minutes (MCAOR 15min, n=6) or 24 hours of reperfusion (MCAOR 24hr, n=2) and compared to blood obtained from a sham surgery (Sham, n=4). Neutrophil CD11b expression was measured in whole blood using flow cytometry methods. Compared to the shams, there was a 70% increase in neutrophil CD11b expression following MCAOR at 15 min (p = 0.06) and a 108% increase following MCAOR at 24 hours (p = 0.03). There was also an 83% and 94% increase of LPS‐stimulated neutrophil CD11b expression at 15 min (p = 0.08) and 24 hours (p = 0.13) of reperfusion. These results indicate that in a mouse model of MCAOR, systemic neutrophils 1) are activated and primed during the first minutes and after 24 hours of reperfusion, and 2) can be easily monitored to assess the effects of new treatments for reperfusion injury after stroke.Supported by NIH NRSA 1 F31 NR010658‐01 (Morrison) NIH HL 58859 (McDonagh) University of Arizona Emmons (Ritter)
Hypercapnia engages parafacial respiratory group (pFRG) neuronal activity coincident with late expiratory motor outflow
Authors: Abdala Ana Paula Lima , Rybak Ilya A , Smith Jeffrey C , Paton Julian F.R. 
Published: June 2021

Recently, we found that suppression of the parafacial respiratory group (pFRG) by bilateral microinjection of isoguvacine (GABAA agonist, 60 nL, 20 mM) abolished late expiratory (late‐E) activity recorded from the abdominal nerve (AbN) during hypercapnia. Thus, we tested the hypothesis that hypercapnia would activate pFRG neurons with late‐E discharge. We recorded phrenic (PN), central vagus (cVN) and AbN outflow (L1) during 7‐10% CO2 while recording from pFRG in the arterially perfused in situ preparation. During normocapnia, AbN exhibited a low amplitude post‐inspiratory discharge only, but a high amplitude late‐E discharge was evoked with 7‐10% CO2. Using a ventral approach to the brainstem, we recorded both population and single unit activities from the caudal half of the pFRG. Two types of neurons were found: (1) tonically firing units that were sensitive to hypercapnia and responded to peripheral chemoreceptor stimulation (n=5) and, (2) rhythmically active units that fired coincidently with AbN late‐E discharge in hypercapnia but were quiescent in the absence of late‐E discharge in AbN during normocapnia (n=5). We conclude that pFRG contains a heterogeneous population of hypercapnia sensitive neurons including a subpopulation of late‐E neurons, which may be the source of the late‐E AbN discharge that emerges during hypercapnia.Research funded by the NIH (RO1 NS057815)
Effect of Hydrogen Sulfide on [Ca2+]i Regulation in Airway Smooth Muscle
Authors: Ryu Alexander , Thompson Michael , Venkatachalem Sathish , Pabelick Christina , Prakash Y S 
Published: June 2021

There is increasing interest in the role of hydrogen sulfide (H2S) as a gasotransmitter similar to nitric oxide and carbon monoxide. In this study, we examined the role of H2S in airway smooth muscle (ASM) inflammation. H2S is produced by the enzymes cystathionine beta‐synthase (CBS) and cystathionine gamma‐lysase (CTH). Both of these enzymes were detected in human ASM by Western blot analysis. In tissues exposed to the pro‐inflammatory cytokine tumor necrosis factor‐a (TNFα) both CTH and CBS expression were upregulated. In ASM strips contracted with 10 µM ACh, only exposure to 1 mM of the H2S donor NaHS induced relaxation. Human ASM cells loaded with fura‐2 demonstrated a dose‐dependent decrease in intracellular calcium concentration ([Ca2+]i) to NaHS (50‐250 μM), in the presence of either 1 μM ACh or 10 μM histamine. However, sodium sulfide (Na2S, 100 µM up to 1 mM) showed no effect on [Ca2+]i. Exposure to 60 mM KCl in the presence of either NaHS or Na2S (50 μM‐3 mM) did not affect [Ca2+]i. Relaxant effects of NaHS or Na2S on ACh‐induced [Ca2+]i elevation were absent when experiments were conducted in zero extracellular Ca2+. These results suggest that H2S relaxes ASM and reduces [Ca2+]i by affecting Ca2+ influx, potentially via voltage‐gated channels, but does not affect sarcoplasmic reticulum Ca2+ release. The relevance of endogenous H2S generation in ASM, and its role in infalmmation needs to be explored further.Supported by the Flight Attendants Medical Research Institute (FAMRI), NIH grant HL74309, and the Department of Anesthesiology, Mayo Clinic.
Activation of Glucose‐6‐Phosphate Dehydrogenase by Depolarization of Membrane Potential Mediates Vascular Smooth Muscle Contraction
Authors: GUPTE Rakhee S , Abe Madoka , Rawat Dhwajbahadur K , Ochi Rikuo , Gupte Sachin A 
Published: June 2021

We have previously demonstrated that inhibition of glucose‐6‐phosphate dehydrogenase (G6PD) evokes relaxation of vascular smooth muscle (VSMC). So, to elucidate the mechanism of relaxation, we examinedwhether G6PD activation affects contraction of VSMC. We found,using ultracentrifugation, two isoforms (62 & 58 KD) of G6PD were present in bovine coronary artery (BCA); the longer (62 KD)isoform was localized in caveolae fraction and the shorter(58 KD) isoform was detected in cytoplasmic fraction. Both isoforms were functionally active; depolarization of the membrane potential to ‐9mV by KCl (30 mM; n=5) increased G6PD activity in the membrane fraction by ~2‐fold. Mechanistic studies revealed that PKCδ mediated activation of G6PD evoked by depolarization in a time‐dependent manner.Silencing of PKCδ in VSMC and HEK293 decreased (P<0.05; n=5) basal activity (0.25 nmol/min/mg protein) of endogenous G6PD and ectopically expressed G6PD in HEK293 (PKCδ−/G6PD+) cells by 50% as compared to cells transfected with non‐targeting siRNA, and in these PKCδ−cells 30mMKClwas unable to activate G6PD. Interestingly, inhibition of G6PD expression in BCA by siRNAand in aorta of G6PD mutated mice, decreased KCl‐induced contractions. In conclusion, activation of G6PD by depolarization of membrane potential plays a pivotal role in mediatingVSMC contraction.This study is supported by AHA and NIH grant# 0435070N and R01HL85352
Histology Challenge: an interactive program for 1st year students
Authors: Dallemagne Catherine , Richardson Neil , Weyand Peter 
Published: June 2021

Our students come from diverse backgrounds. They need flexibility in their learning, and opportunities to review aspects of curriculum they are less confident with. An online teaching and learning programme called the Histology Challenge has been developed to supplement learning experiences offered in several first year anatomy and anatomy&physiology units at QUT. The programme is designed to be integrated with the existing Blackboard sites.The Histology Challenge emphasises the foundation concept that a complex system, such as the human body, can be better understood by examining its simpler components. The tutorial allows students to examine the cells and tissues which ultimately determine structural and functional properties of body organs. The program is interactive, asking students to make decisions and choices, demonstrating an integrated understanding of systemic and cellular aspects. It provides users with the ability to progress at their own pace and to test their understanding and knowledge. For the developer the learning activity can be easily controlled and modified via the use of text files.There are several key elements of this programme, designed to promote specific aspects of student learning. Minimum text is used, instead there is a strong emphasis on instructive artwork and original, high quality histology images presented within a framework that reinforces learning and promotes problem solving skills.
Development and Assessment of Creative Writing Activities within an Interdisciplinary Biotechnology Program
Authors: Clase Kari 
Published: June 2021

Science and technology are changing rapidly resulting in a society that needs graduates who can identify problems and creatively design working solutions. An enmeshing of disciplines within the biological sciences and engineering is creating an interdisciplinary environment in the workplace and academia, which has created a need for interdisciplinary educational environments that enhance creative thinking and innovative problem solving. But how do you teach students creativity and innovation? How do you teach students to work effectively and solve interdisciplinary, ill‐defined problems? Curriculum has been developed and integrated into a multidisciplinary biotechnology program where students are engaged and contribute "hands on" to the pursuit of authentic bioengineering research. The learning goals of the inquiry‐based biotechnology curriculum are to produce students who acquire basic research skills and are able to:Function in interdisciplinary teams to solve ill‐defined problems effectively and creativelyTransfer knowledge across disciplinary contexts.We are exploring the effectiveness of the writing activities to enhance student creativity and increase their knowledge of the nature of science. This poster will describe the writing activities that have been developed to integrate with the hands‐on laboratory activities and the use of calibrated peer review for assessment.
The Interactive Textbook
Authors: Goldberg Harry 
Published: June 2021

The Interactive Textbook is a virtual learning environment that has been designed and developed to serve as a next‐generation textbook. This software integrates multiple media: video, full chapter‐length animation, illustration, simulation, and text into an interface that addresses the needs of students with a variety of learning preferences. One of the major attributes of this system is that it enables faculty to spend less class time relaying facts and more time actively engaging students in discussion of scientific theory and application.The theoretical underpinnings of this system have been tested and shown to be effective in delivering content. The Interactive Textbook is currently being assessed in a variety of university environments. The potential use of this technology in the curriculum will be discussed.
Mechanisms underlying corticosterone mediated inhibition of angiogenesis
Authors: Shikatani Eric A , Haas Tara L 
Published: June 2021

Angiogenesis involves cell proliferation, invasion and migration of endothelial cells. Corticosterone (CORT), elevated in diabetes and metabolic syndrome, is known to be angiostatic, but it's mechanisms of action are unknown. Previously, we found that CORT inhibits matrix metalloproteinase (MMP)‐2 production and activity. We treated rat microvascular endothelial cells with 600 nM CORT for 48 hrs and found a significant decrease in full length MMP‐2 promoter activity using a luciferase reporter assay. This effect was localized to a region between ‐1560 and ‐1386 bp. However, pretreatment of cells with 10 μM RU 486 (glucocorticoid receptor (GR) antagonist) for 2 hrs did not block the CORT mediated inhibition of MMP‐2 production or activation. To observe the effect of CORT on endothelial cell sprouting, we cultured cell spheroids in type‐1 collagen and treated them with CORT for 48 hrs. At 24 hrs CORT treated cells displayed numerous sprouts, similar to controls, but at 48 hrs, sprouts had destabilized and regressed in response to CORT. Our data suggest that the mechanism of CORT‐dependent inhibition of MMP‐2 production may be due to reduced transcription, but that this may not be GR‐mediated. In future studies, we will identify intracellular signals affected by CORT treatment that may contribute to sprout repression. Funding by NSERC & HSFO.Grant Funding SourceNSERC
Dynamic Analysis of Vertebrate Cardiogenesis
Authors: Yang Jennifer , Lansford Rusty , Fraser Scott 
Published: June 2021

Vertebrate heart morphogenesis is a complex process that integrates different structures and cell types driven to interact by genetic and epigenetic factors. We have taken an interdisciplinary approach to studying heart formation by combining the power of molecular genetics with advanced optical imaging within living embryos. We have developed a Tie1‐H2B.eYFP transgenic quail and novel imaging methods that permit dynamic observation and manipulation of vascular development. Avian embryos are ideal for imaging because they are accessible at all stages of development outside of their vertebrate mother, unlike mammals, yet they develop a heart that has four chambers. Our over‐arching goal is to analyze heart morphogenesis and assess the relative roles of epigenetic and genetic mechanisms. Our experimental plan directly tests the hypothesis that flow is a major determinant of cardiac development and offers experimental tools that can be applied in a variety of experimental settings.Grant Funding SourceNIH Cardio
Quantifying relative shape variation in modern human femora and humeri
Authors: Sylvester Adam David , Mahfouz Mohamed R. 
Published: June 2021

Lower limb bones are thought to be more developmentally stable (more symmetric) than upper limb bones, presumably because of the functional importance of locomotion. However, the relative degree of canalization (limits on between‐individual variation) in the limbs is less clear. Here we assess the 3D shape variation between individuals in a sample of modern human femora and humeri.Femora and humeri from 47 human males were CT scanned and 7002 landmarks were distributed across the surface of the bone using a statistical shape atlas (Merkl and Mahfouz, 2007). Each bone was scaled by its first principal component score to remove size and size‐correlated shape, and then by maximum length so that the femora and humeri were the same size. Bone shape variation was assessed as the average root‐sum‐squared distances of bone vertices from their average positions within each element. Bootstrap samples (1000) were used to create distributions of shape variation for each bone type, and distributions were compared using an ANOVA.The analysis reveals that after accounting for differences in size and size‐correlated shape, the humerus is more variable in 3D shape than the femur (p< 0.0001), indicating that the 3D shape of the femur is more canalized than the humerus.Grant Funding SourceNone