PSX-A-16 Late-Breaking: Maternal nutrient restriction and re-alimentation influences liver protein expression in fetal sheep

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 376-377
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kendall C Swanson ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Fetal Liver ◽  
National Research Council ◽  
Trna Synthetase ◽  
Differentially Expressed ◽  
Mass Spectrometry Analysis ◽  
Nutrient Restriction ◽  
Liver Protein ◽  
Fetal Sheep ◽  
Migration Pathways

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on the fetal liver proteome, 48 pregnant ewes with singletons were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, a subset of ewes were fed either CON or 60% NRC requirements (RES). A subset of ewes were euthanized at day 90 of gestation (n = 7/treatment), and fetal liver samples collected. Remaining ewes were maintained on the current diet (CON-CON, n=6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n=7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver proteins were extracted, digested by trypsin and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Proteins were identified and quantified using Proteome Discoverer (v2.5, Thermo Scientific) and differential abundance analysis was performed using ANOVA and post hoc Tukey’s HSD test. Hierarchal clustering analysis showed clustering of treatments by day of gestation. However, differences were also observed between treatments. At day 90 of gestation, 23 proteins were differentially expressed in RES compared with CON among which glycyl tRNA synthetase and pyruvate carboxylase were increased 12% and 10%, respectively (P < 0.03). At day 130 of gestation, 24, 5, and 71 proteins were differentially expressed in CON-RES, RES-CON, and RES-RES, respectively, compared with CON-CON. Carnosine dipeptidase 2 was decreased 7% in CON-RES and rho associated protein kinase and glycogen synthase 2 were increased 20% and 26% in RES-CON and RES-RES, respectively, compared with CON-CON (P < 0.04). These results indicate that nutrient restriction during mid- and late-gestation impacts expression of proteins involved in gluconeogenesis, glycogenesis, and the formation of carnosine, an integral molecule in beta-oxidation, and that re-alimentation alters proteins involved in cell migration pathways. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

PSV-2 Maternal nutrient restriction and re-alimentation influences liver and muscle tissue development and gene expression

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 307-307
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
Kendall C Swanson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Content ◽  
Muscle Development ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Control Diet ◽  
National Research Council ◽  
Pyruvate Dehydrogenase Kinase ◽  
Nutrient Restriction ◽  
Metabolic Factors

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on fetal liver and muscle development, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver and skeletal muscle samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver was analyzed for general tissue morphology, and fetal skeletal muscles were analyzed for lipid accumulation. mRNA expression of growth and metabolic factors were quantified in liver and muscle tissues. Hepatocellular vacuolation was increased in RES-CON and RES-RES compared with CON-CON and CON-RES (P < 0.01). In semitendinosus and triceps brachii, intramyocellular lipid content increased 19% and 15%, respectively, in RES-CON and RES-RES compared with CON-CON and CON-RES (P£0.02) and in longissimus dorsi, lipid content was decreased 7% in CON-RES and RES-RES compared with CON-CON and RES-CON (P=0.01). In liver, insulin-like growth factor binding protein-1, glycogen synthase 2, and pyruvate dehydrogenase kinase 1 expression increased 1.92-fold, 1.45-fold, and 1.47-fold, respectively (P£0.03) in CON-RES and RES-RES compared with RES-CON and CON-CON. In LD, IGF1-R expression increased 3.19-fold in CON-RES and RES-RES compared with RES-CON and CON-CON (P = 0.05). These results demonstrate that maternal nutrient restriction followed by re-alimentation restores liver and muscle gene expression of growth and metabolic factors while negatively impacting liver composition and muscle lipid content potentially leading to altered tissue function and metabolism later in life. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

Effect of hypoxemia on tissue glycogen content and glycolytic enzyme activities in fetal sheep

1997 ◽  
Vol 272 (1) ◽  
pp. R103-R110 ◽  
Author(s):  
L. L. Stratford ◽  
S. B. Hooper
Keyword(s):  
Enzyme Activities ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Glycolytic Enzyme ◽  
Hepatic Glycogen ◽  
Fetal Sheep ◽  
Total Enzyme Activity ◽  
Pregnant Sheep ◽  
Glycogen Stores

We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction in glycogenolytic enzyme activities and/or a depletion of fetal glycogen stores. We compared the effects of short (4 h) and prolonged (24 h) periods of reduced maternal uterine blood flow (RUBF) on glycogen content and on the activities of glucose-6-phosphatase (G-6-Pase), glycogen phosphorylase (GPase), and glycogen synthase (GSase) in selected fetal tissues. RUBF was reduced in 10 pregnant sheep at 135 days of gestation (term approximately 146 days) for either 4 h (n = 5) or 24 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaC2 was decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h. Hepatic glycogen content was significantly reduced at 4 h of RUBF, but was not reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward control values at 24 h. Similarly, hepatic GSase activity tended to decrease at 4 h of RUBF, although the reduction was not quite significant (P = 0.08). We conclude that RUBF causes a reduction of fetal glycogen stores and a reduction in G-6-Pase and GPase activity at 4 h. Fetal tissue glycogen contents were not reduced further at 24 h, compared with 4 h of RUBF, which indicates that fetal glycogenolysis is reduced during this time, probably because of the inhibition of GPase and G-6-Pase. It is not known why the activities of these enzymes are reduced during prolonged RUBF, when circulating epinephrine and norepinephrine concentrations are high.

scholarly journals Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle

2000 ◽  
Vol 167 (3) ◽  
pp. 429-437 ◽  
Author(s):  
JM Brameld ◽  
A Mostyn ◽  
J Dandrea ◽  
TJ Stephenson ◽  
JM Dawson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone Receptor ◽  
Maternal Nutrition ◽  
Fetal Liver ◽  
Mrna Abundance ◽  
Nutrient Restriction ◽  
Fetal Sheep ◽  
Gestation Age ◽  
Igf I ◽  
Metabolisable Energy

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewes up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone receptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes either consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient restricted - approximately 60% of ME requirements, taking into account requirements for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/day (i.e. well fed - approximately 150% of ME requirements) between days 28 and 80 of gestation. All ewes were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 of gestation, five ewes were sampled from each group and fetal tissues taken. There was no difference in fetal body weight or liver weights between groups at either sampling date, or skeletal muscle (quadriceps) weight at 140 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary units), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83;s.e.d. 0.98 arbitrary units, P=0.061 for dietxage interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 days: nutrient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; well fed 6.01;s.e.d. 1.09 arbitrary units, P=0.061 for diet). Nutrient restriction had no effect on hepatic GHR mRNA abundance, but re-feeding of previously nutrient-restricted fetuses increased GHR mRNA compared with continuously well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 140 days: restricted/re-fed 115.7; well fed 89.4;s.e.d. 10.13 arbitrary units, P=0.047 for dietxage interaction). In fetal skeletal muscle, IGF-I mRNA abundance was not influenced by maternal nutrition and decreased with gestation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after 60 days of re-feeding (restricted/re-fed 7.77; well fed 13.72;s.e.d. 1.98 arbitrary units, P<0.001 for dietxage interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and/or GHR in the fetus which may subsequently relate to altered organ and tissue function.

scholarly journals Moderate nutrient restriction of beef heifers alters expression of genes associated with tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum by day 50 of gestation1

2019 ◽  
Vol 3 (2) ◽  
pp. 855-866 ◽  
Author(s):  
Matthew S Crouse ◽  
Joel S Caton ◽  
Robert A Cushman ◽  
Kyle J McLean ◽  
Carl R Dahlen ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Transcript Abundance ◽  
Differentially Expressed ◽  
Nutrient Restriction ◽  
Functional Categories ◽  
Beef Heifers ◽  
Nutritional Treatment ◽  
Tissue Metabolism ◽  
Expression Of Genes ◽  
And Function

Abstract We hypothesized that a moderate maternal nutrient restriction during the first 50 d of gestation in beef heifers would affect transcript abundance of genes associated with tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum. Angus-cross heifers were estrus synchronized and assigned at breeding to one of two dietary treatments (CON- 100% of nutrient requirements to gain 0.45 kg/d; RES- 60% of CON). At day 50 of gestation, 14 heifers were ovariohysterectomized, and fetal liver, muscle, and cerebrum were collected. Transcriptome analysis via RNA-seq was conducted on the Illumina HiSeq 2500 platform using 50-bp paired-end reads at a depth of 2 × 10.4M reads/sample. Bioinformatic analysis was performed using the Tuxedo Suite and ontological analysis with DAVID 6.8. For fetal liver, muscle, and cerebrum, a total of 548, 317, and 151 genes, respectively (P &lt; 0.01) were differentially expressed, of which 201, 144, and 28 genes, respectively were false discovery rate protected (FDR; q &lt; 0.10). Differentially expressed genes were screened for fit into functional categories of pathways or ontologies associated with known impacts on tissue metabolism, accretion, and function. In fetal liver, five functional categories of interest (n = 125 genes) were affected by nutritional treatment: metabolic pathways, protein kinase, nucleosome core, mRNA splicing, and complement/coagulation cascades, of which 105 genes were upregulated in RES. In fetal muscle, three functional categories of interest (n = 106 genes) were affected by nutritional treatment: skeletal muscle, embryogenesis, and signaling cascades, of which 64 genes were upregulated in RES. In fetal cerebrum, three functional categories of interest (n = 60 genes) were affected by nutritional treatment: hippocampus and neurogenesis, metal-binding, and cytoskeleton, of which 58 genes were upregulated in RES. These results demonstrate that a moderate maternal nutrient restriction during the first 50 d of gestation in beef heifers alters transcript abundance of genes potentially impacting tissue metabolism, accretion, and function in fetal liver, muscle, and cerebrum. Furthermore, these results indicate that affected categories are tissue-specific and moderate maternal nutrient restriction generally increases expression of genes in fetuses from RES fed dams. Finally, these data lay the foundation upon which further research that identifies phenotypic responses to changes in these pathways may be elucidated.

scholarly journals PSIV-16 Maternal Nutrient Restriction Followed by Re-alimentation Alters Distinct Metabolic Pathways in Sheep Offspring

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 284-285
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
Kendall C Swanson ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Control Diet ◽  
National Research Council ◽  
Enrichment Analysis ◽  
Postnatal Growth ◽  
Pentose Phosphate ◽  
Nutrient Restriction ◽  
Pathway Enrichment Analysis ◽  
Phenylalanine Metabolism ◽  
Isoleucine Metabolism

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on offspring metabolism, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver, longissimus dorsi, and blood metabolites were analyzed using LC-MS/MS at Metabolon Inc. Pathway enrichment analysis was conducted using MetaboAnalyst 4.0. In liver, muscle, and blood, 64, 44, and 34 pathways were enriched between treatments at day 130 gestation and 10, 6, and 11 pathways were enriched at day 90 gestation, respectively. Arginine and proline metabolism; primary bile acid biosynthesis; and valine, leucine, and isoleucine biosynthesis were the most highly enriched pathways in RES compared with CON in liver, muscle, and blood, respectively. Additionally, the pentose phosphate pathway; valine, leucine, and isoleucine metabolism; and phenylalanine metabolism were the most highly enriched pathways in RES-CON compared with CON-CON in liver, muscle, and blood, respectively. In liver, ribulose 5-phosphate, xylulose 5-phosphate, and ribose 5-phosphate were decreased 1.82-, 1.54-, and 2.38-fold, respectively in RES-CON compared with CON-CON (P ≤ 0.05). Total triacylglycerols were increased 3.04-fold in muscle and decreased 1.57-fold in blood in RES-CON and RES-RES compared with CON-CON and CON-RES (P ≤ 0.05). Mid-gestational nutrient restriction and subsequent re-alimentation altered distinct metabolic amino acid, carbohydrate, and lipid pathways, potentially altering postnatal growth. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus

2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Lu ◽  
Hai-Zhu Xing ◽  
Nian-Yun Yang
Keyword(s):  
Insulin Resistance ◽  
Liver Injury ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Proteomic Analysis ◽  
Acute Liver Injury ◽  
Liver Cells ◽  
Differentially Expressed ◽  
Liver Protein ◽  
Differentially Expressed Proteins

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage

scholarly journals Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep

2021 ◽  
Vol 22 (14) ◽  
pp. 7654
Author(s):  
Chelsie B. Steinhauser ◽  
Colleen A. Lambo ◽  
Katharine Askelson ◽  
Gregory W. Burns ◽  
Susanta K. Behura ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Killer Cell ◽  
National Research Council ◽  
Enrichment Analysis ◽  
Nutrient Utilization ◽  
Gene Set Enrichment Analysis ◽  
Nutrient Restriction ◽  
Placental Development ◽  
Gene Set Enrichment ◽  
Pregnant Sheep

Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35–135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.

Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model

2011 ◽  
Vol 38 (6) ◽  
pp. 665-672 ◽  
Author(s):  
A. Sørensen ◽  
D. Holm ◽  
M. Pedersen ◽  
A. Tietze ◽  
B. Stausbøl-Grøn ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Bold Mri

scholarly journals Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries

2014 ◽  
Vol 307 (2) ◽  
pp. H134-H142 ◽  
Author(s):  
Praveen Shukla ◽  
Srinivas Ghatta ◽  
Nidhi Dubey ◽  
Caleb O. Lemley ◽  
Mary Lynn Johnson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Coronary Arteries ◽  
National Research Council ◽  
Muscle Cells ◽  
Nutrient Restriction ◽  
Epoxyeicosatrienoic Acid ◽  
Coronary Smooth Muscle ◽  
Maternal Undernutrition ◽  
Current Activation

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway.

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