bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Patterns After Injury In Regenerating Young and Old Skeletal Muscle
Authors: Wang Fenyu , Hill Jonathon T. , Thomson David 
Published: April 2020

Healthy skeletal muscle repair occurs through proper regulation of gene expression in many cell types within the regenerating muscle niche, including skeletal muscle, macrophages, fibroblasts, etc. However, the ability to repair muscles is compromised in old muscle, and the mechanisms for this are not fully understood. To further investigate factors leading to this age‐related defect in repair and regeneration, we conducted RNA sequencing on tibialis anterior muscle tissue from young (Y; 5 mo.) and old (O; 24 mo.) mice basally and at day 3, day 7, and day 10 after cardiotoxin‐induced injury. Principle component analysis demonstrated a general delay in global gene expression changes over the 10 day regeneration period in O muscles. Gene Set Enrichment Analysis (GSEA) of Hallmark Pathways showed that in Y muscles, inflammation and immune‐related pathways were upregulated at Day 3 followed by upregulated myogenesis‐related expression on days 7–10. In contrast, O muscles upregulated hypoxia‐ and metabolism‐related pathways at day 3, and showed continued upregulation of inflammation‐ and apoptosis‐ related gene expression through days 7–10, suggesting failure to resolve the inflammatory and cell stress response during the later regenerative period. This was associate with delayed Pax7 expression in the O muscles. As expected, upregulated expression of Wnt/beta‐catenin signaling pathway components, which are heavily involved in myogenesis, was dysregulated in old regenerating muscles. Our analysis indicates that disrupted gene regulation patterns post injury are a pivotal factor in the defective regenerative capacity of old muscles.Support or Funding InformationThis research was supported by a BYU Gerontology Award.
Collagen and Elastin Disarray Mechanisms Mediating Aortic Stiffness in Aging Pre‐Menopausal Female Monkeys.
Authors: Babici Denis , Kudej Raymond , McNulty Tara , Zhang Jie , Oydanich Marko , Berkman Tolga , Nishimura Koichi , Vatner Dorothy E. , Vatner Stephen F. 
Published: April 2020

Whereas collagen and elastin content have been widely studied as mechanisms for mediating increased aortic stiffness with aging, collagen and elastin disarray has been less well studied, not only in all aging models, but most particularly in aging pre‐menopausal females. The current investigation compared collagen and elastin disarray in the aorta in aging, 24±1 years old, premenopausal female monkeys (M. Fascicularis and M. Mulatta) with disarray in young female monkeys (6 ± 1 years old). The non‐human primate model is unique for these studies, since most other aging animal models do not go through menopause. Collagen/elastin ratio and disarray were increased in the old, pre‐menopausal females compared to the young females in the thoracic aorta, but even more in the abdominal aorta, and the most in the iliac artery. For example, compared to values in the thoracic aorta of young females, the collagen/elastin ratio increased in the thoracic aorta of old female monkeys by 169%, and by 397% in the iliac artery of the old females. Compared to values in the thoracic aorta of young females, the disarray of elastin fibers increased by 106% in the thoracic aorta of the old female monkeys and by 350% in the iliac artery of the old female monkeys. Compared to values in the thoracic aorta of young females, the disarray of collagen fibers increased by 148% in the thoracic aorta of the old females and by 378% in the iliac artery of the old female monkeys. Compared to values in the thoracic aorta of young females, the number of breaks in elastin fibers increased by 158% in the thoracic aorta of the old females and by 883% in the iliac artery of the old female monkeys. Compared to values in the thoracic aorta of young females, the number of breaks in collagen fibers increased by 105% in the thoracic aorta of the old females and by 390% in the iliac artery of the old female monkeys. Thus, old pre‐menopausal female monkeys exhibit enhanced mechanisms of vascular stiffness. These mechanisms were increased in the thoracic aorta, but significantly more increased in the iliac artery.Support or Funding InformationStudy supported by National Institutes of Health grants R21 AG053514; R01 HL119464; R01 HL137405; R01 HL102472; R01 HL106511; R01 HL130848; R01 HL137368; UL1TR003017;
Effects of Western Diet on Histological Characteristics of Muscle in Leptin‐Resistant Pigs
Authors: Yankaway Raizel B. , Spooner Heather C. , Hernandez Gabriella V. , Smith Victoria A. , Burrin Douglas G. , Maj Magdalena , Manjarin Rodrigo , Blank Jason M. 
Published: April 2020

Leptin‐resistant pigs offer a promising model for the study of non‐alcoholic fatty liver disease (NAFLD), particularly in pediatric populations. Muscle is a large and metabolically active tissue that may play an important role in the storage and metabolism of lipid during the development of NAFLD.In this study, 10‐day old piglets were fed either a control diet (CON) (n=8) or a Western diet containing high levels of fructose, saturated fat and cholesterol (HFF) (n=12) every 6 hours for 70 days. Half of the pigs in each diet group were supplemented with a blend of probiotics containing Pediococcus, Lactobacillus and Bacillus. Longissimus dorsi muscle was collected on day 70 for immunohistochemistry and triacylglyceride (TG) quantification. Tissue sections were stained for lipid content with Oil Red O and muscle cells were fiber‐typed based on myosin heavy chain isoforms.Muscle tissue from pigs fed HFF diets had higher total TG content, but a lower number of Oil Red O positive cells and a lower lipid staining intensity of these cells. HFF diet also caused a reduction in the fraction of type I (slow‐twitch) muscle fibers.In summary, this staining pattern suggests that the muscle from HFF fed animals may have an increased accumulation of lipid in extramyocellular depots rather than within muscle cells and a decreased capacity to oxidize lipids. Such shifts in muscle metabolic characteristics may contribute to the progression of metabolic disease.Support or Funding InformationThe project was funded by ARI#58873, STRIDE#35466, and the William and Linda Frost Fund.
Hypoxia‐Induced Syndecan 1 Shedding in Placental Trophoblasts is Associated with Increased Peroxide
Authors: Mahmoudi Elena , Cates Courtney , Chapman Heather , George Eric Matthew 
Published: April 2020

Preeclampsia is one of the most common obstetrical disorders, affecting ~5% of pregnancies. It is one of the leading causes of maternal and fetal morbidity and mortality, as well as premature birth. While the origins of preeclampsia are obscure, it is believed that many cases are due to placental insufficiency and resulting ischemia/hypoxia. While many of the factors released by the ischemic placenta are known, the full scope of the molecular effects of ischemia on the placenta are not known. We have recently demonstrated that hypoxia causes shedding of the placental extra cellular matrix in vitro and in vivo, particularly the glycoprotein syndecan 1. It has also been reported that vascular ECM shedding can be affected by reactive oxygen species. Therefore, we wished to test the hypothesis that oxidative stress is the mediator of placental syndecan 1. We treated placental trophoblast derived cells (BeWo) for 24 hours with oxygen conditions mimicking healthy (8%) or ischemic (1%) placentas. To determine the effect of hypoxia on peroxide production, we used the peroxide indicator amplex red. In response to hypoxic conditions, amplex fluorescence was significantly increased (6728 ± 196 vs 8201 ± 501 AU, p<0.05), which was attenuated with the peroxide scavenger apocynin (4626 ± 100 AU, p>0.05). In response to hypoxia, SDC1 released from BeWos increased significantly (175 ± 10 vs 280 ± 13 pg/ml, p<0.05). There was no effect of the peroxide scavenger apocynin in normoxic conditions, but there was a significant reduction (185 ± 10 pg/ml, p<0.05) in hypoxic conditions. These data suggest that peroxide is a key mediator of hypoxia‐induced shedding of SDC‐1, and could play a key role in ECM shedding in placental ischemia in vivo. Future studies will examine the in vivo effects of peroxide scavenging on SDC shedding as well as its effects on other ECM components.Support or Funding InformationThis work was supported in part by NIH grants P01HL51971, P20GM104357, and R01HL137791
Vitamin D Impacts Nrf‐2 Signaling and Antioxidation Pathways that Modulate Cellular Aging
Authors: Sabir Zhela L. , Livingston Sarah , Whitfield G. Kerr , Haussler Mark R. , Jurutka Peter 
Published: April 2020

Recent studies suggest that the biologically active form of vitamin D, 1,25‐dihydroxyvitamin D (1,25D), plays a role in potentially delaying the aging process, functions as an anti‐carcinogenic agent, and also prevents oxidative damage. 1,25D binding to the vitamin D receptor (VDR) promotes heterodimerization of VDR with the retinoid X receptor (RXR) to stimulate transcription of numerous vitamin D target genes. The VDR‐RXR complex controls transcriptional activity targeting various tissues such as the kidney and colon, regulates immune defenses, and controls cellular proliferation. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf‐ 2), is a transcriptional regulator that stimulates expression of genes encoding antioxidant enzymes via a DNA sequence referred to as an antioxidant‐responsive element (ARE). Nutraceuticals such as urolithin‐A have been proposed to play a role in this pathway. The current study was designed to investigate how vitamin D‐VDR signaling influences Nrf‐2 activity. Therefore, we utilized an ARE‐luciferase reporter plasmid to measure Nrf‐2 activity in human embryonic kidney cells (HEK‐293) in the presence of VDR. Our results indicate that VDR does not target genes with an ARE sequence directly. Instead, when cells were transfected with both Nrf‐2 and VDR, Nrf‐2 activity was significantly inhibited in a 1,25D‐ and VDR‐dependent manner. However, when cells were treated with urolithin‐A alone, or with vitamin D in conjunction with urolithin‐A, a nutraceutical that is hypothesized to cooperate with vitamin D, Nrf‐2 activity was upregulated. Additionally, real‐time quantitative polymerase chain reaction (qPCR) was employed to test the expression levels of GCLC and HMOX1 (two Nrf‐2 target genes), in the absence and presence of 1,25D, to assess if the mRNA expression results were consistent with the luciferase reporter assays. Thus, the current study reveals that VDR likely targets Nrf‐2 genes indirectly by influencing the activity of the Nrf‐2 transfactor. Collectively, our results demonstrate, for the first time, that VDR either binds directly to the Nrf‐2 protein to inhibit its activity, or 1,25D‐VDR represses Nrf‐2 gene expression resulting in a diminution of Nrf‐2 protein production. Modulation of Nrf‐2 activity by the vitamin D pathway appears to have a regulatory role in anti‐oxidation and cellular aging pathways.Support or Funding InformationNational Institutes of Health; grant numbers: DK033351 and CA140285.
A Hybrid Approach to Learning Endocrine Physiology: Investigating the Efficacy of Using “MicroVids” to improve student learning
Authors: Pierre-Louis Gandhy , Brainard Robert 
Published: April 2020

IntroductionWith advances in technology, many lectures are now recorded and uploaded online for re‐viewing by students. However, lectures are long ranging from 50–120 minutes and students need to devote a large amount of time in order to review lecture, which can deter students from viewing recorded lectures. Therefore, we proposed creating short videos (MicroVids) reviewing only one specific concept from lecture and embedding the MicroVid into the printed notes via QR code, so that as students review the printed notes, they have a quick and easily accessible option for viewing professor‐explained concepts without searching the entire recorded lecture for the desired material.ObjectivesTo investigate the efficacy of utilizing MicroVids as a tool to improve student learning of the endocrine system.MethodsA series of 8 MicroVids were created reviewing concepts in the endocrine section of Anatomy and Physiology 1. The MicroVids were uploaded to YouTube and the URLs for each video was linked to a QR code that students could either click on to access the MicroVid (electronic notes) or scan with a QR code reader while reviewing their notes. Students (n=18, experimental group) taking an AP1 class during the Fall 2019 semester were given 8 MicroVids as supplemental material. After one week of access to each group’s MicroVids, students were given a survey to gather student feedback. Exam results from endocrine questions on their summative assessment was compared a control group of students taking AP1 the same semester as those that received Microvids and also compared to students who took AP1 Fall 2018.OutcomeThis approach garnered an overwhelming positive feedback. Two major themes from surveyed students were: 1) the MicroVids were easily accessible and 2) they helped students capture information they missed from their lecture notes. In the class that received the Microvids, 94% of the students watched the videos and 61% of students reported that it helped them succeed in their summative assessment. Additionally, while there was no statistically significant difference in exam grades between the class of students who watched the MicroVids versus the students of the control group, there was a modest improvement on the grasp of the endocrine system between poor test performers in the experimental group as compared to the poor test performers in the control group (an average 2.8 percentage points difference). While modest, the observation that poor test performers in the experimental group outperformed their control counterparts on their assessment is consistent with other reports that demonstrated similar positive learning outcomes when an active learning strategy was implemented in the classroom.
Hybrid Genome Assembly of a Regenerative Chordate
Authors: Sumner Jack Thomas , Wax Sarah , Andrasz Cassidy , Anderson Paul , Keeling Elena , Davidson Jean 
Published: April 2020

Modern genome sequencing technologies open new avenues for research on biological processes in non‐model organisms. Colonial ascidians are a diverse group of invertebrate chordates capable of whole body regeneration, an unusual trait that is absent from vertebrates. Although genomic data are available for a few related species, there exist no such data for the highly regenerative species Botrylloides violaceus. Using a de novo hybrid assembly approach, we present the first draft of the B. violaceus genome sequence. By integrating short read and long read sequencing technologies, genome assembly becomes cost‐effective and easily accessible. Comparative genomic analysis between B. violaceus and other chordate genomes reveals insights into the evolution of gene families implicated in regeneration and development.Support or Funding InformationWarren J. Baker and Robert D. Koob Endowments, California Polytechnic State University; The Frost Fund, College of Science and Mathematics, California Polytechnic State University
Early Post‐Natal Maternal Effects on Voluntary Exercise, Maximal Aerobic Capacity, and Associated Traits in Mice
Authors: Cadney Marcell D. , Schwartz Nicolas , McNamara Monica , Schmill Margaret , Castro Alberto , Hillis David , Garland Theodore 
Published: April 2020

During the suckling period, many mammals progress through numerous developmental milestones, including critical periods of the central nervous system, musculoskeletal system, and cardiovascular system – each an important element of physical activity and exercise capacity. In a novel experimental mouse model, four replicate lines were selectively bred for ~90 generations for high voluntary wheel‐running behavior (high‐runner; HR) while four non‐selected Control (C) lines were also maintained. As a result of selection, HR mice run approximately 3‐fold the distances of C mice on a daily basis. Various other physiological and behavioral differences have also evolved in the HR lines, including higher maximal oxygen consumption (VO2max). The aim of the present study was to assess the role of the maternal environment during the birth‐weaning period in the expression of the many differences between HR and C lines using a cross‐fostering paradigm. Cross‐fostering HR mice to C dams (and vice versa) at birth and until weaning allowed us to determine the relative contribution of genetic and early environmental factors in shaping the HR phenotype. Mice were weaned three weeks after birth, housed in same‐sex cages of four, and adult testing began at approximately six weeks of age with measurement of VO2max, daily wheel running over a six‐day period, food consumption, home‐cage activity, body fat composition, and organ masses following dissection. As expected, HR mice ran approximately ~3‐fold more revolutions/day on wheels than their C counterparts. Preliminary analyses show that rearing by an HR dam has a negative effect on adult wheel running in females. This result suggests that the maternal environment provided by HR dams during the suckling period may play a role in the selection limit observed in HR lines.Support or Funding InformationNSF GRFP
“(−)‐Epicatechin reduces inflammation biomarkers in plasma and ameliorates cardiac fibrosis in a female rat model of pre‐HFpEF”
Authors: Bustamante-Pozo Moises Muratt , Garate-Carrillo Alejandra Alejandra , VILLARREAL FRANCISCO , Ito Bruce Robert , CEBALLOS GUILLERMO , Ramirez-Sanchez Israel 
Published: April 2020

The consumption of polyphenolic compounds, specifically flavonoids, have been associated with beneficial impacts on cardiovascular health. Flavonoids are found in plants and fruits such as cacao, berries, grapes and tea leaves. Cacao seeds contain high levels of the flavanol (−)‐ epicatechin. (−)‐Epicatechin (Epi) is therefore present in products such as dark chocolate or cocoa powder and has proven to have beneficial effects on the cardiovascular system. In the heart, it can reduce infarct size and apparently, myocardial fibrosis. Thus, we aimed to examine the potential of Epi to reduce myocardial fibrosis and improving passive and active left ventricular function and structure in an aging female rat model of pre‐HFpEF characterized by low estrogen levels, excess weight and hypertension. Female, 18‐month‐old, Fischer F344 rats were allocated into an ovariectomy + 10% fructose (OVF), and ovariectomy + 10% fructose + Epi (OVFE) (n=9–10/group). Epi treatment (1 mg/kg/day) was provided by gavage during a 30‐day period (from 21 to 22 months of age) while control animals received water. Left ventricular (LV) structure/function was assessed monthly by echocardiography. At 22 months of age, animals were anesthetized, and LV function was evaluated using a Millar conductance catheter. Histological measures of chamber morphometry, inflammation and collagen density (fibrosis) were also obtained. With treatment, no major structural and functional modifications were detected by echocardiography or by conductance‐catheter based hemodynamics. Passive left ventricular pressure volume curves were significantly right shifted with Epi while circumferential epicardial strains were reduced. The histological analysis of collagen quantification using Sirius red indicated that Epi treatment significantly reduced overall levels of myocardial fibrosis. Epi also significantly reduced plasma levels of pro‐fibrotic and pro‐inflammatory cytokines. In conclusion, Epi appears capable of reducing cardiac fibrosis in an animal model of pre‐HFpEF which correlate with reductions in cytokine plasma levels. However, reductions in tissue fibrosis did not translate into major modifications in passive or active chamber structure and function. This model may serve to understand the role that estrogen depletion and weight gain may have in the development of HFpEF.Support or Funding InformationFunding was provided by the Department of Defense PR150090 and National Institutes of Health DK98717, AG47326 to F.V. and Consejo Nacional de Ciencia y Tecnologia, Mexico to G. C.
Screening assay using an epigenetic modulator library identifies I10 that promotes melanin synthesis in B16/F10 melanoma cells
Authors: Hwang Yun Jeong , Boo Yong Chool 
Published: April 2020

Skin pigmentation is affected by genetic, epigenetic and many other factors, and contributes to human beauty and health. Recent studies reported that certain epigenetic modulators altered the gene expression of enzymes involved in melanin synthesis, suggesting that those drugs may be potentially useful in treating skin hyper‐ or hypo‐pigment disorders. The aim of the present study is to find a drug candidate from an epigenetic drug library that can promote melanin synthesis in cells. Each drug was examined for the stimulatory effects on melanin synthesis in B16F10 murine melanoma cells. Of 141 drugs tested, I10 was selected because it most effectively stimulated melanin synthesis. Like forskolin, an adenylate cyclase activator, I10 increased the mRNA and protein levels of tyrosinase enzyme, the rate‐limiting enzyme involved in melanin synthetic pathway. However, unlike forskolin, I10 did not stimulate the expression of microphthalmia‐associated transcription factor (MITF), a key regulator of melanin synthesis. Although much further research is needed, this current study suggests that I10 may promote cellular melanin synthesis through a mechanism that is distinct from that of forskolin, and it may be a new drug candidate for the treatment of skin hypo‐pigmentation disorders such as vitiligo.Support or Funding InformationThis work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. 2019R1I1A2A01045132).
The role of NEGR1 in the formation of lipid droplets
Authors: An Dayoung , Joo Yeonhee , Kim Hyejin 
Published: April 2020

Neuronal growth regulator 1 (NEGR1) is a membrane raft‐associated protein, which has been spotlighted as a new locus related to human obesity. We previously identified that NEGR1 interact with Niemann‐Pick diseases, type C2 (NPC2) that plays a key role in intracellular cholesterol trafficking, suggesting a new role of NEGR1 in the intracellular lipid transport. In this study, we report that the level of lipid droplets (LD) reduced in NEGR1‐overexpressiong 3T3L‐1 cells compared to vector‐transfected controls. Moreover, we observed that the intracellular LD level was higher in primary adipocytes obtained from NEGR1−/− mice than those from wild‐type mice. In addition, the expression level of LD‐associated protein, perilipin‐2/ADRP, increased in white adipose tissues of NEGR1‐deficient mice, although we could not detect any direct interaction between NEGR1 and ADRP proteins. Altogether, we suggest that NEGR1 is involved in LD formation possibly by regulating the intracellular lipid trafficking.Support or Funding InformationKorea research foundation