bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trichlorophenol Induced Nephrotoxicity in Isolated Rat Renal Cortical Cells
Authors: Rankin Gary O. , Nguyen Vy , Hicks W. Mason , Brown Kathleen C. , Dial Mason , Leader Tori , Valentovic Monica A. , Anestis Dianne 
Published: June 2021

Trichlorophenols (TCPs) are wood preservatives and intermediates in the synthesis of numerous pesticides. They appear in the environment as manufacturing byproducts and during the chlorination of drinking and waste water. TCPs are also metabolites of chlorinated compounds, such as chlorobenzenes and chlorophenoxy acids. Aquatic toxicity induced by these compounds has been studied in some detail, but few studies have focused on mammalian toxicity. The purpose of this study was to examine the nephrotoxic potential of four TCPs (2,3,4‐; 2,3,6‐, 2,4,5‐; and 2,4,6‐TCP) in an in vitro model using isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC (~4 million cells/ml; 3 ml) were incubated with shaking at 37°C under a 95% oxygen/5% carbon dioxide atmosphere with a TCP (0 – 1.0 mM) or vehicle (dimethyl sulfoxide) for 60 min. General cytotoxicity was determined by assessing trypan blue exclusion of IRCC, measuring changes in lactate dehydrogenase (LDH) release, and quantitating ATP levels. LDH release was increased only at 1.0 mM for 2,3,6‐ and 2,4,6‐TCP. 2,3,4‐TCP increased LDH release at 0.5 mM or greater concentrations. However, 2,4,5‐TCP increased LDH release at 0.1 mM or greater concentrations. ATP levels were decreased at 1.0 mM for all compounds, at 0.5 mM for 2,3,4‐TCP and at all 2,4,5‐TCP concentrations. Therefore, the general order of decreasing nephrotoxic potential was 2,4,5‐TCP > 2,3,4‐TCP >2,3,6‐ and 2,4,6‐TCP.Support or Funding InformationSupported in part by NIH grant P20GM103434.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Doxorubicin Renal Cytotoxicity and Protection by Resveratrol (RES)
Authors: Valentovic Monica , Getty Morghan , Brown Katie C. 
Published: June 2021

The cancer chemotherapeutic agents Doxorubicin (DOX, Adriamycin), is part of the treatment regimen for breast, Hodgkin and Non‐Hodgkin lymphomas, small cell lung cancer and acute lymphoid leukemia. Doxorubicin clinical usage is associated with cardiomyopathy and renal impairment. The mechanism for doxorubicin mediated renal toxicity has remained elusive. Resveratrol (RES) is a phytoalexin found in many fruits including grapes, blueberries, chocolate and peanuts. Antioxidant and anticancer properties have been reported for RES in cell culture and in vivo. This study tested the hypothesis that RES will reduce DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial cells (HK‐2) and that RES will attenuate DOX cytotoxicity by preserving mitochondrial function and reducing oxidative stress. HK‐2 cells were grown for 48 h. Cells were next pre‐incubated for 1 h with 0 (DMSO) or 5 or 7.5 uM RES followed by a 24 h co‐incubation with 0–5 uM DOX. All results were obtained from 3 independent experiments. Western analysis probed for protein carbonylation was used as an indicator of oxidative stress. Mitochondrial function was assessed using a Seahorse XFp system. Prior to examining mitochondrial function, cell number and substrate concentrations were optimized based on the manufacturer's recommendations. Mitochondrial Stress Test was conducted following the treatments described above and each well was normalized to protein. Western blot was conducted on whole cell lysate for SIRT1 and PGC1alpha. Viability was assessed using MTT leakage. RES did not alter cell viability as indicated by comparable MTT values between DMSO and RES groups (p>0.05). DOX was cytotoxic to HK‐2 cells within 24 h. Pretreatment with RES provided protection from DOX to HK‐2 cells. Mitochondrial respiration assessed as oxygen consumption rate (OCR) was diminished by DOX. DOX impaired mitochondria function within 24 h and RES provided protection. Further studies are needed to better characterize DOX mediated changes in mitochondria and reversal by RES.Support or Funding Information(Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Chromosome 14 in the Genetic Basis for Endurance Exercise Capacity and Responses to Training in Mice
Authors: Massett Michael P. , Avila Joshua J. , Kim Seung Kyum 
Published: June 2021

A significant quantitative trait locus (QTL) for exercise capacity and a suggestive QTL for the change in exercise capacity were identified previously on mouse Chromosome 14 (Chr 14). The aim of this study was to investigate the role of Chr 14 in endurance exercise capacity and responses to training in mice. Exercise capacity and training responses were measured in chromosome substitution strain (CSS) mice derived from PWD/PhJ (PWD) and C57BL/6J (B6) inbred strains, denoted as B6.PWD14. These mice carry Chr 14 from the PWD donor inbred strain on the genetic background of a host B6 inbred strain. Twelve‐week‐old male and female mice from each strain (B6, PWD, B6.PWD14) were assigned to sedentary control (SED) or exercise training (EX) groups (n=6/group/sex). All mice completed a graded exercise test before and after the exercise‐training period to determine endurance exercise capacity. Responses to training were calculated from the difference in exercise capacity between post‐ and pre‐training graded exercise tests. EX mice completed a 4‐week training program consisting of treadmill running 5 days/week, 60 min/day at a final intensity equivalent to approximately 65% of the maximal work‐load (speed and incline) attained during the graded exercise test. Overall, there were significant effects of sex and strain on body mass and exercise capacity (pre and post), but only a significant effect of sex on responses to training in EX mice. In male mice, there were no significant differences in endurance exercise capacity or responses to training between B6 and B6.PWD14 mice. In contrast, female B6.PWD14 mice had higher pre‐ and post‐training endurance exercise capacity than female B6 mice. However, there were no significant differences between mice from these strains for responses to training. These data demonstrate that PWD alleles on Chr 14 significantly affect pre‐ and post‐training endurance exercise capacity in a sex‐specific manner. Furthermore, these data suggest that Chr 14 contains genetic factors influencing endurance exercise capacity, but not the responses to training in these strains of mice.Support or Funding InformationSupported by NIH R01 HL085918, APS William Townsend Porter Pre‐doctoral Fellowship (JA), and Texas A & M University Institute for Advanced Study (TIAS).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Acute Effects of Aerobic Exercise on Arterial Stiffness and Wave Reflection in Young Men and Young Premenopausal Women
Authors: Lim Jisok , Kim Han‐Kyul , Hwang Chueh‐Lung , Yoo Jeung‐Ki , Perez Hannah , Handberg Eileen M. , Christou Demetra 
Published: June 2021

Arterial stiffness and wave reflection are associated with increased risk for cardiovascular disease (CVD), while aerobic exercise is known to decrease CVD risk. The effects of chronic aerobic exercise training on arterial stiffness and wave reflection have been extensively studied, but data on the acute effects of aerobic exercise on these measures are primarily based on men and are limited and conflicting. The purpose of this study was to examine the sex‐specific acute vascular responses to high‐intensity interval training (HIIT), moderate‐intensity continuous training (MICT) and low‐intensity continuous training (LICT) in young adults. Thirty healthy adults, 15 young men and 15 premenopausal women (21.5±0.4 vs. 21.4±0.7 years of age, means ± SE, P =0.9) participated in this randomized crossover study. The SphygmoCor Xcel device (AtCor medical) was employed to assess arterial stiffness using carotid to femoral pulse wave velocity (cfPWV) and wave reflection using augmentation index (AIx). Measures of cfPWV and AIx were obtained prior to exercise (PreE), following the end of a single bout of HIIT, MICT and LICT on the treadmill (PostE), and following recovery from exercise. HIIT consisted of 4 × 4‐min intervals at 90% peak heart rate (HRpeak) interspersed by recovery bouts at 70% HRpeak for a total of 40 min, whereas MICT and LICT consisted of 47 min at 70% and 50% HRpeak, respectively. cfPWV remained unchanged in response to a single bout of exercise, regardless of exercise intensity or sex (5.5±0.1 vs. 5.5±0.1 vs. 5.4±0.1 m/s, PreE vs. PostE vs. recovery; P=0.2 for main effect of time). AIx decreased following recovery compared with PreE and PostE (P≤0.003), but this response was not influenced by exercise intensity or sex (10.3±1.7 vs. 9.0±1.7 vs. 5.0±1.5 %, PreE vs. PostE vs. recovery; P<0.0001 for main effect of time; P=0.8 for sex × exercise × time). In conclusion, exercise intensity and sex do not modulate central arterial stiffness and wave reflection following a single bout of aerobic exercise. Central arterial stiffness is unaffected by acute exercise, whereas wave reflection decreases following recovery from exercise.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aldosterone‐sensitive HSD2 neurons in the nucleus of the solitary tract: gene expression and axonal projections in mice
Authors: Geerling Joel C. , Resch Jon M. , Lowell Brad B. , Peltekian Lila , Narayan Sowmya V. 
Published: June 2021

Dietary sodium deficiency elevates aldosterone, which in turn stimulates a unique group of neurons in the nucleus of the solitary tract (NTS). In the adult mouse brain, these NTS neurons alone express the enzyme 11‐beta‐hydroxysteroid dehydrogenase type 2 (HSD2), a hallmark of aldosterone‐sensitive cells. Here, we add detailed information about HSD2 neurons in mice, which initially were characterized in rats. First, we confirm that HSD2‐immunoreactive neurons in mice are found exclusively in the NTS. Next, using in situ hybridization, we show that these neurons robustly express Hsd11b2, the mineralocorticoid receptor (Nr3c2), vesicular glutamate transporter 2 (Slc17a6), the transcription factor Phox2b, and the angiotensin II receptor 1a (Agtr1a). Conversely, they do not express protein markers for cholinergic and monoaminergic neurons or mRNA transcripts for the peptides galanin (Gal), dynorphin (Pdyn), or angiotensinogen (Agt), which are abundant in the surrounding NTS. Next, in Hsd11b2‐Cre mice, we use Cre‐dependent axon labeling to refine conventional axon tracing data from rats. HSD2 neurons project their axons into the ipsilateral reticular formation, where they course rostrally past the trigeminal motor nucleus before turning dorsally towards the parabrachial complex (PB). There, the axons form dense terminal fields in the pre‐locus coeruleus (pLC) and an adjoining part of the medial PB subnucleus and arborize laterally in a subregion of the central lateral PB subnucleus. In addition, some axons course rostrally through the midbrain reticular formation, into the medial forebrain bundle, and ultimately form a dense terminal field in a subregion of the ventrolateral bed nucleus of the stria terminalis (BSTvL) that is homologous to the rat fusiform subnucleus. En route to the BSTvL, small numbers of axons branch and form boutons in the parasubthalamic nucleus, suprafornical lateral hypothalamic area, central nucleus of the amygdala, and paraventricular hypothalamic nucleus. Finally, using dual retrograde tracing, we found that projections to PB and BSTvL originate from separate subsets of HSD2 neurons. While their long‐range projection to BSTvL likely promotes sodium appetite, their axonal projections to PB and other sites may alter the taste of sodium and mediate other behavioral correlates of sodium depletion such as nausea, anhedonia, or fatigue.Support or Funding InformationK08 NS099425 (JCG); Aging, Mind, and Brain Institute, University of Iowa (JCG); F32 DK103387 (JMR); R01 DK075632, R01 DK096010, R01 DK089044, R01 DK111401, P30 DK046200, P30 DK057521 (BBL)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Calcium influx at hyperpolarized membrane potentials modulates depolarization‐triggered exocytosis in bovine chromaffin cells.
Authors: Fomina Alla F. , Yang Lukun 
Published: June 2021

Perturbations in Ca2+ entry via neuronal transient receptor potential (TRP) and ORAI family proteins have been shown to alter synaptic transmission, and suggested to play a role in several neurodegenerative diseases including Huntington's, Alzheimer's and Parkinson's diseases. Specific mechanisms by which of TRP/ORAI channels modulate synaptic signaling are not completely understood. To determine the role of Ca2+ influx trough non‐voltage gated Ca2+ channels in regulation of neurotransmitter release, we investigated effects of modulation of Ca2+ influx at hyperpolarized voltages on exocytosis in bovine chromaffin cells using a combination of imaging and electrophysiological techniques. We found that a small inwardly directed membrane current whose amplitude was dependent on the concentration of extracellular Ca2+ and Na+, was present at resting membrane potential. Augmentation of this current either by hyperpolarization (from −50 mV to −90 mV) or stimulation with bradykinin (1 μM), a catecholamine secretagogue, elevated cytosolic Ca2+ concentration at hyperpolarized potentials and facilitated exocytotic responses triggered by short depolarizations (<500 ms in duration). Exocytotic responses triggered by long depolarizations (>500 ms in duration) were suppressed at hyperpolarized holding potentials. Reversal of Na+/Ca2+ exchanger by removal of Na+ from bath solution did not cause depolarization‐independent exocytosis at −50 mV holding potential. Membrane hyperpolarization from −50 mV to −90 mV in the absence of direct Na+/Ca2+ exchanger activity evoked depolarization‐independent exocytosis. Our findings provide first experimental evidence that in neuroendocrine cells perturbation in Ca2+ influx at negative voltages with physiologically relevant stimuli significantly modulates exocytotic responses to depolarization‐triggered Ca2+ entry via voltage‐gated Ca2+ channels, and that Ca2+ influx via native Ca2+ channels operating at negative voltages is functionally coupled with Na+/Ca2+ exchanger.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Organismal Sex is a Major Determinant of Phenotypic and Molecular Changes Caused by Genetic Inactivation of the Mitochondria‐specific Deacetylase SIRT3
Authors: Roos Carolyn M. , Hagler Michael A. , Zhang Bin , Fujimoto Hirokazu , Miller Jordan D. 
Published: June 2021

Sirtuin 3 (SIRT3)—a deacetylase localized to the mitochondria—deacetylates a number of mitochondria‐specific proteins, including the mitochondrial antioxidant enzyme MnSOD. We previously reported that genetic inactivation of SIRT3 impairs endothelial function and increases pro‐osteogenic markers in early stages of atherosclerosis. While recent data suggest that the molecular and phenotypic effects of SIRT enzyme inactivation can act in a highly sex‐dependent manner, we have not systematically studied sex differences in our unique mouse strains. Here, we report our first effort to explore the presence of molecular and phenotypic sex differences following inactivation of SIRT3 in hypercholesterolemic mice. We used female and male Ldlr−/−/ApoB100/100 mice that were either wild‐type (LA‐SIRT3+/+) or null for SIRT3 (LA‐SIRT3−/−). Following 3 months of western diet feeding, we assessed endothelial function of aorta using isolated organ bath chambers and measured changes in gene expression using qRT‐PCR. We did not observe sex differences at baseline in hypercholesterolemic mice, as endothelium‐dependent relaxation to acetylcholine (ACH) was similar between female LA‐SIRT3+/+ and their male LA‐SIRT3+/+ littermates (61.1%±2.2, 57.9%±2.7; respectively). Interestingly, genetic inactivation of SIRT3 did not impair responses to ACH in female LA‐SIRT3−/− mice (61.1%±4.2), whereas responses to ACH were modestly impaired in male LA‐SIRT3−/− mice (53.9%±1.9). Consistent with SIRT3's role as a post‐translational protein modifier, expression of MnSOD was unchanged across all sexes and genotypes. Expression of genes related to pathophysiological changes in atherosclerotic plaques did change in a highly sex‐dependent manner, however, as osterix gene expression levels (related to plaque calcification) were markedly increased in male LA‐SIRT3−/− compared to their sex‐matched wild‐type littermates and to their female counterparts. Surprisingly, while female LA‐SIRT3−/− mice showed dramatic increases in expression of interleukin 6 (related to inflammation) compared to their wild‐type littermates, male LA‐SIRT3−/− had robust reductions in expression in interleukin 6 compared to their LA‐SIRT3+/+ littermates. Collectively, these data suggest there are significant, sex‐dependent molecular and phenotypic effects of SIRT3 inactivation in hypercholesterolemic mice, which may also drive a paradoxical dissociation between pro‐osteogenic and pro‐inflammatory signaling under conditions of mitochondrial dysfunction.Support or Funding InformationNHLBI R01‐HL111121This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phrenic afferent projections to the cervical spinal cord in spinal intact and spinal injured rats
Authors: Turner Sara , Schuster Cassandra , Fusco Anna , Cotto Alejandra , Pignataro Megan , Sunshine Michael , Fuller David 
Published: June 2021

The phrenic nerve contains both myelinated and unmyelinated afferent projections. Relatively little is known, however, regarding the spinal distribution of these sensory projections. Accordingly, our first goal was to create a map of phrenic afferent projections throughout the cervical spinal cord. Afferents were traced via prolonged phrenic nerve soak with Cascade Blue (CB) in adult Sprague‐Dawley rats. Spinal tissues were harvested, sectioned (40μm) from C2–C7, and processed with routine immunochemical methods. Extensive labeling of afferent projections was observed throughout the ipsilateral dorsal horn (laminae II and III) and intermediate grey region (laminae IV and V) in segments C2–C6. Phrenic afferent projections were crossed the spinal midline in 13% of the tissue sections, and were occasionally observed to reach the contralateral dorsal horn (laminae III). Robust phrenic motoneuron (PhrMN) labeling was observed from C3–C5, and PhrMN dendrites projected across the spinal midline in 30% of tissue sections from C3–C5. Our second objective was to determine if high cervical spinal cord injury (SCI) induced anatomical plasticity in the phrenic sensorimotor system. The phrenic nerve was traced using the same CB method in Sprague‐Dawley rats at 12 weeks following lateral hemisection of the C2 spinal cord. Preliminary analysis indicates that following SCI, phrenic afferents and PhrMN dendrites project across the spinal midline at approximately the same frequency as in spinal‐intact rats (p>0.36). However, we noted that the likelihood of observing phrenic afferent projections extending to the region of the ipsilateral phrenic motor nucleus (laminae VIII‐IX) was increased after SCI (p<0.05). By combining CB labeling with Choline acetyltransferase (ChAT) immunostaining, we verified the presence of laminae VIII‐IX phrenic afferents by observing CB‐positive and ChAT negative fibers. We conclude that phrenic sensory afferent projections 1) are prominent in the ipsilateral C3–C5 dorsal horn and intermediate grey region, 2) can project to the contralateral C3–C5 dorsal horn, and 3) undergo remodeling after high cervical SCI.Support or Funding InformationSPARC OT2 OD023854 (DDF), 1 R01 NS080180‐01A1 (DDF)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using Brains to Inspire Minds: A Unique Outreach Collaboration with the Boston Museum of Science
Authors: Babcock Katharine Jane , Kong Elizabeth , Zumwalt Ann C. 
Published: June 2021

The Department of Anatomy and Neurobiology at Boston University School of Medicine has recently undertaken an exciting collaboration with the Hall of Human Life (HHL) at the Museum of Science, Boston to engage the general public in a dialogue about the human brain. This partnership is unique in that the scientists and the museum staff work together to develop demonstrations that neither group would have the resources to produce on their own. In this initiative we use post‐mortem human brains to get the attention of museum visitors and pique their curiosity. Visitors are encouraged to ask questions and drive discussions based on their own interests, while educators adapt their language as needed when interacting with audiences of differing age groups. Topics vary from how information is relayed to and from the brain, to specific interests such as recent public health concerns surrounding concussion in sports. In addition to human tissue, the exhibit also includes human anatomical models and dissections of simpler nervous systems (e.g. rat, mouse, gerbil, fish, and fruit fly) to stimulate comparative and functional neuroanatomical discussions. The main objective is to cultivate a broad‐based, easily accessible learning experience that mirrors the HHL's mission to “inspire all who enter to think, learn, and question.”Support or Funding InformationAAA Education Outreach GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.