Publications by authors named "Heewon Seo"

Background: The creatine-creatine kinase-phosphocreatine (Cr-CK-PCr) system maintains intracellular ratios of ATP/ADP for support of cellular functions and has been characterized at the placental-uterine interface of rodents, primates, swine and sheep, and thus may support fetal development. This study determined effects of dietary supplementation of creatine (Cr) to gestating gilts on fetal development, the number and ratio of primary and secondary muscle fibers, and on protein expression in endometrium and fetal biceps-femoris muscle, respectively in fetal pigs on d 60 and d 90 of gestation.

Methods: Reproductively mature gilts were synchronized to estrus using Matrix, observed for estrus (d 0), and artificially inseminated 12 h and 36 h later.

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The creatine (Cr) biosynthesis pathway buffers ATP in metabolically active tissues. We investigated whether sex of fetus and day of gestation influence Cr in endometrial and conceptus tissues from gilts on Days 60 and Day 90 (n = 6 gilts/day) of gestation. Uterine and conceptus tissues associated with one male and one female fetus from each gilt were analyzed for creatine, mRNAs, and proteins for Cr biosynthesis.

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  • Understanding the diffuse invasion of glioblastoma cells is crucial for addressing tumor aggressiveness and resistance to treatment, which negatively impacts patient prognosis.
  • The study utilizes a novel computational method to analyze GBM xenografts, distinguishing human tumor cells from the mouse tumor microenvironment (TME), resulting in a detailed overview of 15 tumor cell programs linked to invasion pathways.
  • The findings suggest targeted interventions on tumor and TME components could lead to improved therapies by revealing compensatory mechanisms that might aid in developing more effective combination treatments.
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  • HIV-1 relies on its unspliced RNA (HIV-1 RNA) for two key functions: as a template for producing proteins needed for virion production and as the genetic material packaged into new viral particles.
  • The virus generates two primary forms of this RNA (1G and 3G), which differ by only a couple of nucleotides, specifically at their 5' ends, and the efficiency of translation for these RNAs is influenced by their 5' untranslated region (UTR) structures.
  • Research indicates that 3G RNA is translated more effectively than 1G RNA due to its favorable structural configuration; however, when the structures of the two RNAs are made similar in mutants, they
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In Brief: The trophectoderm of the elongating conceptuses of cattle, sheep, and pigs secrete high amounts of interferons that increase or induce the expression of interferon-stimulated genes (ISGs) in the endometrium. Research concerning ISGs, performed from 1995 through 2023, is reviewed in this manuscript.

Abstract: Expression of the classical interferon (IFN) stimulated genes (ISGs) increases in the endometrial stroma and glandular epithelium (GE) through activation of signal transducer and activator of transcription (STAT) signaling in response to the secretion of IFN tau (IFNT) and IFN gamma (IFNG) by the conceptuses of ruminants, including cattle and sheep, and pigs, respectively.

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Background: Tissue non-specific alkaline phosphatase (TNSALP; encoded by the ALPL gene) has a critical role in the postnatal regulation of phosphate homeostasis, yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown. This study tested the hypothesis that progesterone (P4) and/or interferon tau (IFNT) regulate TNSALP activity during pregnancy in sheep.

Methods: In Exp.

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  • Embryonic mortality in pigs mainly occurs during two critical periods: when embryos elongate and during the development of the uterine-placental interface.
  • The study hypothesizes that low levels of ATP in the embryo and uterine tissues contribute to conceptus loss, suggesting that creatine plays a key role in ATP production.
  • Analyses showed increased expression of genes related to creatine metabolism in elongating pig embryos, indicating that ATP production is crucial during periods of high energy demand for implantation and placentation.
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Advances in molecular profiling have facilitated generation of large multi-modal datasets that can potentially reveal critical axes of biological variation underlying complex diseases. Distilling biological meaning, however, requires computational strategies that can perform mosaic integration across diverse cohorts and datatypes. Here, we present mosaicMPI, a framework for discovery of low to high-resolution molecular programs representing both cell types and states, and integration within and across datasets into a network representing biological themes.

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  • Interferon-gamma (IFNG) is a key pro-inflammatory cytokine produced by pig embryos during early pregnancy, crucial for implantation and conceptus survival.
  • The study found IFNG present in both the embryo and the endometrial lining on Day 15 of pregnancy, indicating potential mechanisms for its transport across the uterine lining.
  • Results suggest that extracellular vesicles (EVs) play a significant role in transporting IFNG from the conceptus into the endometrium, enhancing communication for successful pregnancy continuation.
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  • - The study analyzes early bovine placentation using immunohistochemistry to observe the histological differences at the utero-placental interface during key gestational days (21, 31, 40, and 67).
  • - Key findings include various types of PAG-positive cells, including mononuclear, multinucleated, and syncytial cells, indicating complex cellular dynamics in the uterine lining.
  • - The research highlights the variability in the utero-placental interface, suggesting that different sections can yield different insights into placentation, challenging the perception of a uniform structure.
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Mammals differ regarding their placentae, but in all species placental trophoblasts interact intimately with the uterine endometrium to mediate the transfer of nutrients from the mother to the embryo/fetus through the closely juxtaposed microcirculatory systems of the uterus and placenta. Placentation in ruminants is intermediate between the non-invasive type, as observed in the epitheliochorial placenta of pigs, and the invasive type, as observed in the haemochorial placentae of mice and humans. In ruminants, placental trophoblast cells invade uterine endometrial tissue, but invasion is believed to be limited to the endometrial luminal epithelium (LE).

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Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases, and other products from the mother to the embryo and fetus. Placentation differs histologically among species, but all types of placentation share the common trait of utilizing highly complex cell-to-cell and tissue-to-tissue morphological and biochemical interactions to remodel the uterine-placental interface. An elegant series of electron microscopy (EM) images supports the classification of ovine placentation as synepitheliochorial, because uterine luminal epithelial (LE) cells are maintained at the uterine-placental interface through incorporation into trophoblast syncytial plaques.

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Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix (ECM) interactions leading to assembly of integrin adhesion complexes (IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus (embryo/fetus and associated placental membranes) development.

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The placenta requires high levels of adenosine triphosphate to maintain a metabolically active state throughout gestation. The creatine-creatine kinase-phosphocreatine system is known to buffer adenosine triphosphate levels; however, the role(s) creatine-creatine kinase-phosphocreatine system plays in uterine and placental metabolism throughout gestation is poorly understood. In this study, Suffolk ewes were ovariohysterectomized on Days 30, 50, 70, 90, 110 and 125 of gestation (n = 3-5 ewes/per day, except n = 2 on Day 50) and uterine and placental tissues subjected to analyses to measure metabolites, mRNAs, and proteins related to the creatine-creatine kinase-phosphocreatine system.

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  • Most embryonic loss in pigs occurs early in gestation (before day 30), but supplementing with L-arginine (Arg) may improve the survival and development of embryos in gilts.
  • In a study, gilts were fed diets with either Arg or L-alanine from days 14 to 30 of gestation, focusing on the effects of Arg on various reproductive metrics.
  • Results showed that Arg supplementation significantly enhanced the number of viable fetuses, placental development, and overall fetal metrics compared to the control, indicating potential benefits for reproductive success in pigs.
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The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells.

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Highly proliferative cells rely on one carbon (1C) metabolism for production of formate required for synthesis of purines and thymidine for nucleic acid synthesis. This study was to determine if extracellular serine and/or glucose and fructose contribute the production of formate in ovine conceptuses. Suffolk ewes (n = 8) were synchronized to estrus, bred to fertile rams, and conceptuses were collected on Day 17 of gestation.

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Ruminant conceptuses that elongate and attach to the uterine luminal epithelium (LE) to establish pregnancy require a large amount of adenosine triphosphate (ATP). The creatine (Cr)-creatine kinase (CK)-phosphocreatine (PCr) system re-generates ATP in dividing and migrating cells such as the conceptus trophectoderm cells. However, little is known about metabolism of Cr within uterine and conceptus tissues in livestock species during early gestation.

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  • The one-carbon metabolism (OCM) pathway supplies essential components for nucleic acid synthesis and plays a role in gene regulation, with serine hydroxymethyltransferase 2 (SHMT2) being a key enzyme in this process.
  • Using a morpholino antisense oligonucleotide (MAO) to inhibit SHMT2 translation in ovine trophectoderm (oTr) cells resulted in decreased cell proliferation and migration, affecting their development.
  • Intrauterine injection of MAO-SHMT2 in ewes showed a trend toward lower pregnancy rates due to impaired oTr cell function, linking SHMT2's role in the OCM pathway to the survival and development of ov
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Roles of fructose in elongating ovine conceptuses are poorly understood, despite it being the major hexose sugar in fetal fluids and plasma throughout gestation. Therefore, we determined if elongating ovine conceptuses utilize fructose via metabolic pathways for survival and development. Immunohistochemical analyses revealed that trophectoderm and extra-embryonic endoderm express ketohexokinase and aldolase B during the peri-implantation period of pregnancy for conversion of fructose into fructose-1-phosphate for entry into glycolysis and related metabolic pathways.

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Although pain-related excessive fear is known to be a key factor in chronic pain disability, which involves the anterior cingulate cortex (ACC), little is known about the downstream circuits of the ACC for fear avoidance in pain processing. Using behavioral experiments and functional magnetic resonance imaging with optogenetics at 15.2 T, we demonstrate that the ACC is a part of the abnormal circuit changes in chronic pain and its downstream circuits are closely related to modulating sensorimotor integration and generating active movement rather than carrying sensory information.

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Introduction: The uterus and placenta transport water during pregnancy recognition signaling, conceptus implantation, and placental development/placentation. This is likely influenced by aquaporins (AQPs) in the reproductive tract. This study determined mRNA and cell-type specific expression of AQP 1, 5, 8, and 9 proteins in the porcine uterus and placenta.

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  • During the peri-implantation phase of pig pregnancy, the trophectoderm uses glucose for growth, limiting pyruvate availability for the TCA cycle.
  • Researchers hypothesized that trophectoderm cells generate TCA cycle components through anaplerosis, specifically by converting glutamine to α-ketoglutarate via glutaminolysis.
  • Findings reveal that trophectoderm cells increase glutaminase levels for glutamine conversion, and when incubated with 13C-glutamine, they show higher accumulation of various TCA cycle intermediates, especially in the absence of glucose, indicating they rely on glutamine to sustain TCA cycle function.
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Background: Fetal-placental development depends on a continuous and efficient supply of nutrients from maternal blood that are acquired by exchange through the placenta. However, the placenta is a low permeability barrier, and effective transport of substances depends on specific transport mechanisms. Active transport requires that ions or nutrients be moved against an electrical and/or concentration gradient.

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Conceptus elongation and early placentation involve growth and remodeling that requires proliferation and migration of cells. This demands conceptuses expend energy before establishment of a placenta connection and when they are dependent upon components of histotroph secreted or transported into the uterine lumen from the uterus. Glucose and fructose, as well as many amino acids (including arginine, aspartate, glutamine, glutamate, glycine, methionine, and serine), increase in the uterine lumen during the peri-implantation period.

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