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Fuller W Bazer - One of the best experts on this subject based on the ideXlab platform.
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The many faces of interferon tau
Amino Acids, 2015Co-Authors: Fuller W Bazer, Greg A. Johnson, Wei Ying, Xiaoqiu Wang, Kathrin A. Dunlap, Beiyan Zhou, Guoyao WuAbstract:Interferon tau (IFNT) was discovered as the pregnancy Recognition Signal in ruminants, but is now known to have a plethora of physiological functions in the mammalian uterus. The mammalian uterus includes, from the outer surface to the lumen, the serosa, myometrium and endometrium. The endometrium consists of the luminal, superficial glandular, and glandular epithelia, each with a unique phenotype, stromal cells, vascular elements, nerves and immune cells. The uterine epithelia secrete or selectively transport molecules into the uterine lumen that are collectively known as histotroph. Histotroph is required for growth and development of the conceptus (embryo and its associated extra-embryonic membranes) and includes nutrients such as amino acids and glucose, enzymes, growth factors, cytokines, lymphokines, transport proteins for vitamins and minerals and extracellular matrix molecules. Interferon tau and progesterone stimulate transport of amino acids in histotroph, particularly arginine. Arginine stimulates the mechanistic target of rapamycin pathway to induce proliferation, migration and protein synthesis by cells of the conceptus, and arginine is the substrate for synthesis of nitric oxide and polyamines required for growth and development of the conceptus. In ruminants, IFNT also acts in concert with progesterone from the corpus luteum to increase expression of genes for transport of nutrients into the uterine lumen, as well as proteases, protease inhibitors, growth factors for hematopoiesis and angiogenesis and other molecules critical for implantation and placentation. Collectively, the pleiotropic effects of IFNT contribute to survival, growth and development of the ruminant conceptus.
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Pregnancy Recognition Signaling mechanisms in ruminants and pigs
Journal of animal science and biotechnology, 2013Co-Authors: Fuller W BazerAbstract:Maternal Recognition of pregnancy refers to the requirement for the conceptus (embryo and its associated extra-embryonic membranes) to produce a hormone that acts on the uterus and/or corpus luteum (CL) to ensure maintenance of a functional CL for production of progesterone; the hormone required for pregnancy in most mammals. The pregnancy Recognition Signal in primates is chorionic gonadotrophin which acts directly on the CL via luteinizing hormone receptors to ensure maintenance of functional CL during pregnancy. In ruminants, interferon tau (IFNT) is the pregnancy Recognition Signal. IFNT is secreted during the peri-implantation period of pregnancy and acts on uterine epithelia to silence expression of estrogen receptor alpha and oxytocin receptor which abrogates the oxytocin-dependent release of luteolytic pulses of prostaglandin F2-alpha (PGF) by uterine epithelia; therefore, the CL continues to produce progesterone required for pregnancy. Pig conceptuses secrete interferon delta and interferon gamma during the peri-implantation period of pregnancy, but there is no evidence that they are involved in pregnancy Recognition Signaling. Rather, pig conceptuses secrete abundant amounts of estrogens between Days 11 to 15 of pregnancy required for maternal Recognition of pregnancy. Estrogen, likely in concert with prolactin, prevents secretion of PGF into the uterine venous drainage (endocrine secretion), but maintains secretion of PGF into the uterine lumen (exocrine secretion) where it is metabolized to a form that is not luteolytic. Since PGF is sequestered within the uterine lumen and unavailable to induce luteolysis, functional CL are maintained for production of progesterone. In addition to effects of chorionic gonadotrophin, IFNT and estrogens to Signal pregnancy Recognition, these hormones act on uterine epithelia to enhance expression of genes critical for growth and development of the conceptus.
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Uterine Histotroph and Conceptus Development: Select Nutrients and Secreted Phosphoprotein 1 Affect Mechanistic Target of Rapamycin Cell Signaling in Ewes
Biology of Reproduction, 2011Co-Authors: Fuller W Bazer, Guoyao Wu, Greg A. Johnson, Gwonhwa SongAbstract:Interferon tau (IFNT), the pregnancy Recognition Signal in ruminants, abrogates the uterine luteolytic mechanism to ensure maintenance of function for the corpora lutea to produce progesterone (P4). IFNT also suppresses expression of classical IFN-stimulated genes by uterine lumenal epithelium (LE) and superficial glandular (sGE) epithelium but, acting in concert with progesterone, affects expression of a multitude of genes critical to growth and development of the conceptus. The LE and sGE secrete proteins and transport nutrients into the uterine lumen necessary for conceptus development, pregnancy Recognition Signaling, and implantation. Secretions include arginine and secreted phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to polyamines or act directly to activate the mechanistic target of rapamycin cell Signaling pathway to stimulate proliferation, migration, and mRNA translation in trophectoderm cells. SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce focal adhesion assembly, adhesion, and migration of conceptus trophectoderm cells during implantation. Thus, arginine and SPP1 mediate growth, migration, cytoskeletal remodeling, and adhesion of trophectoderm essential for pregnancy Recognition Signaling and implantation. This minireview focuses on components of histotroph that affect conceptus development in the ewe.
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Select Nutrients in the Ovine Uterine Lumen. IX. Differential Effects of Arginine, Leucine, Glutamine, and Glucose on Interferon Tau, Ornithine Decarboxylase, and Nitric Oxide Synthase in the Ovine Conceptus
Biology of Reproduction, 2011Co-Authors: Robert C. Burghardt, Guoyao Wu, Thomas E. Spencer, Greg A. Johnson, Fuller W BazerAbstract:Nutrients are primary requirements for development of conceptuses (embryo and extraembryonic membranes), including protein synthesis. We have shown that arginine (Arg), leucine (Leu), and glucose stimulate protein synthesis through phosphorylation of MTOR Signaling molecules, thereby increasing proliferation of ovine trophectoderm cells. This study determined whether Arg, Leu, glutamine (Gln), and glucose influence gene expression and protein synthesis in explant cultures of ovine conceptuses recovered from ewes on Day 16 of pregnancy. Conceptuses were deprived of select nutrients and then cultured with either Arg, Leu, Gln, or glucose for 18 h, after which they were analyzed for abundance of MTOR, RPS6K, RPS6, EIF4EBP1 (also known as 4EBP1), IFNT, NOS2, NOS3, GCH1, and ODC1 mRNAs and proteins. Levels of MTOR, RPS6K, RPS6, and EIF4EBP1 mRNAs were not affected by treatment with any of the select nutrients. Similarly, expression of IFNT, NOS2, NOS3, and ODC1 mRNAs were not different. Interestingly, GCH1 mRNA levels increased in response to Arg treatment. Importantly, Arg, Leu, Gln, and glucose increased the abundance of phosphorylated MTOR, RPS6K, RPS6, and EIF4EBP1 proteins as well as NOS and ODC1 proteins, but only Arg increased the abundance of IFNT protein. These findings indicate that Arg, Leu, Gln, and glucose stimulate translation of mRNAs to increase synthesis of proteins through phosphorylation and activation of components of the MTOR Signaling pathway. Increases in abundance of IFNT protein (the pregnancy Recognition Signal), NOS2, NOS3 and GCH1 for conversion of Arg to nitric oxide, and ODC1 for synthesis of polyamines are all important for growth and development of the ovine conceptus during pregnancy.
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Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation
Physiological Genomics, 2009Co-Authors: M. Carey Satterfield, Fuller W Bazer, Gwonhwa Song, Kelli J. Kochan, Penny K. Riggs, Rebecca M. Simmons, Christine G. Elsik, David L. Adelson, Huaijun Zhou, Thomas E. SpencerAbstract:Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy Recognition Signal, and initiates implantation. Blastoc...
Rongfu Wang - One of the best experts on this subject based on the ideXlab platform.
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trim14 inhibits cgas degradation mediated by selective autophagy receptor p62 to promote innate immune responses
Molecular Cell, 2016Co-Authors: Meixin Chen, Qingcai Meng, Puping Liang, Lian He, Yubin Zhou, Yongjun Chen, Junjiu Huang, Rongfu WangAbstract:Summary Cyclic GMP-AMP synthase (cGAS) is an essential DNA virus sensor that triggers type I interferon (IFN) Signaling by producing cGAMP to initiate antiviral immunity. However, post-translational regulation of cGAS remains largely unknown. We report that K48-linked ubiquitination of cGAS is a Recognition Signal for p62-depdendent selective autophagic degradation. The induction of TRIM14 by type I IFN accelerates cGAS stabilization by recruiting USP14 to cleave the ubiquitin chains of cGAS at lysine (K) 414. Knockout of TRIM14 impairs herpes simplex virus type 1 (HSV-1)-triggered antiviral responses in a cGAS-dependent manner. Due to impaired type I IFN production, Trim14 −/− mice are highly susceptible to lethal HSV-1 infection. Taken together, our findings reveal a positive feedback loop of cGAS Signaling generated by TRIM14-USP14 and provide insights into the crosstalk between autophagy and type I IFN Signaling in innate immunity.
Guoyao Wu - One of the best experts on this subject based on the ideXlab platform.
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The many faces of interferon tau
Amino Acids, 2015Co-Authors: Fuller W Bazer, Greg A. Johnson, Wei Ying, Xiaoqiu Wang, Kathrin A. Dunlap, Beiyan Zhou, Guoyao WuAbstract:Interferon tau (IFNT) was discovered as the pregnancy Recognition Signal in ruminants, but is now known to have a plethora of physiological functions in the mammalian uterus. The mammalian uterus includes, from the outer surface to the lumen, the serosa, myometrium and endometrium. The endometrium consists of the luminal, superficial glandular, and glandular epithelia, each with a unique phenotype, stromal cells, vascular elements, nerves and immune cells. The uterine epithelia secrete or selectively transport molecules into the uterine lumen that are collectively known as histotroph. Histotroph is required for growth and development of the conceptus (embryo and its associated extra-embryonic membranes) and includes nutrients such as amino acids and glucose, enzymes, growth factors, cytokines, lymphokines, transport proteins for vitamins and minerals and extracellular matrix molecules. Interferon tau and progesterone stimulate transport of amino acids in histotroph, particularly arginine. Arginine stimulates the mechanistic target of rapamycin pathway to induce proliferation, migration and protein synthesis by cells of the conceptus, and arginine is the substrate for synthesis of nitric oxide and polyamines required for growth and development of the conceptus. In ruminants, IFNT also acts in concert with progesterone from the corpus luteum to increase expression of genes for transport of nutrients into the uterine lumen, as well as proteases, protease inhibitors, growth factors for hematopoiesis and angiogenesis and other molecules critical for implantation and placentation. Collectively, the pleiotropic effects of IFNT contribute to survival, growth and development of the ruminant conceptus.
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Uterine Histotroph and Conceptus Development: Select Nutrients and Secreted Phosphoprotein 1 Affect Mechanistic Target of Rapamycin Cell Signaling in Ewes
Biology of Reproduction, 2011Co-Authors: Fuller W Bazer, Guoyao Wu, Greg A. Johnson, Gwonhwa SongAbstract:Interferon tau (IFNT), the pregnancy Recognition Signal in ruminants, abrogates the uterine luteolytic mechanism to ensure maintenance of function for the corpora lutea to produce progesterone (P4). IFNT also suppresses expression of classical IFN-stimulated genes by uterine lumenal epithelium (LE) and superficial glandular (sGE) epithelium but, acting in concert with progesterone, affects expression of a multitude of genes critical to growth and development of the conceptus. The LE and sGE secrete proteins and transport nutrients into the uterine lumen necessary for conceptus development, pregnancy Recognition Signaling, and implantation. Secretions include arginine and secreted phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to polyamines or act directly to activate the mechanistic target of rapamycin cell Signaling pathway to stimulate proliferation, migration, and mRNA translation in trophectoderm cells. SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce focal adhesion assembly, adhesion, and migration of conceptus trophectoderm cells during implantation. Thus, arginine and SPP1 mediate growth, migration, cytoskeletal remodeling, and adhesion of trophectoderm essential for pregnancy Recognition Signaling and implantation. This minireview focuses on components of histotroph that affect conceptus development in the ewe.
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Select Nutrients in the Ovine Uterine Lumen. IX. Differential Effects of Arginine, Leucine, Glutamine, and Glucose on Interferon Tau, Ornithine Decarboxylase, and Nitric Oxide Synthase in the Ovine Conceptus
Biology of Reproduction, 2011Co-Authors: Robert C. Burghardt, Guoyao Wu, Thomas E. Spencer, Greg A. Johnson, Fuller W BazerAbstract:Nutrients are primary requirements for development of conceptuses (embryo and extraembryonic membranes), including protein synthesis. We have shown that arginine (Arg), leucine (Leu), and glucose stimulate protein synthesis through phosphorylation of MTOR Signaling molecules, thereby increasing proliferation of ovine trophectoderm cells. This study determined whether Arg, Leu, glutamine (Gln), and glucose influence gene expression and protein synthesis in explant cultures of ovine conceptuses recovered from ewes on Day 16 of pregnancy. Conceptuses were deprived of select nutrients and then cultured with either Arg, Leu, Gln, or glucose for 18 h, after which they were analyzed for abundance of MTOR, RPS6K, RPS6, EIF4EBP1 (also known as 4EBP1), IFNT, NOS2, NOS3, GCH1, and ODC1 mRNAs and proteins. Levels of MTOR, RPS6K, RPS6, and EIF4EBP1 mRNAs were not affected by treatment with any of the select nutrients. Similarly, expression of IFNT, NOS2, NOS3, and ODC1 mRNAs were not different. Interestingly, GCH1 mRNA levels increased in response to Arg treatment. Importantly, Arg, Leu, Gln, and glucose increased the abundance of phosphorylated MTOR, RPS6K, RPS6, and EIF4EBP1 proteins as well as NOS and ODC1 proteins, but only Arg increased the abundance of IFNT protein. These findings indicate that Arg, Leu, Gln, and glucose stimulate translation of mRNAs to increase synthesis of proteins through phosphorylation and activation of components of the MTOR Signaling pathway. Increases in abundance of IFNT protein (the pregnancy Recognition Signal), NOS2, NOS3 and GCH1 for conversion of Arg to nitric oxide, and ODC1 for synthesis of polyamines are all important for growth and development of the ovine conceptus during pregnancy.
Thomas E. Spencer - One of the best experts on this subject based on the ideXlab platform.
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Select Nutrients in the Ovine Uterine Lumen. IX. Differential Effects of Arginine, Leucine, Glutamine, and Glucose on Interferon Tau, Ornithine Decarboxylase, and Nitric Oxide Synthase in the Ovine Conceptus
Biology of Reproduction, 2011Co-Authors: Robert C. Burghardt, Guoyao Wu, Thomas E. Spencer, Greg A. Johnson, Fuller W BazerAbstract:Nutrients are primary requirements for development of conceptuses (embryo and extraembryonic membranes), including protein synthesis. We have shown that arginine (Arg), leucine (Leu), and glucose stimulate protein synthesis through phosphorylation of MTOR Signaling molecules, thereby increasing proliferation of ovine trophectoderm cells. This study determined whether Arg, Leu, glutamine (Gln), and glucose influence gene expression and protein synthesis in explant cultures of ovine conceptuses recovered from ewes on Day 16 of pregnancy. Conceptuses were deprived of select nutrients and then cultured with either Arg, Leu, Gln, or glucose for 18 h, after which they were analyzed for abundance of MTOR, RPS6K, RPS6, EIF4EBP1 (also known as 4EBP1), IFNT, NOS2, NOS3, GCH1, and ODC1 mRNAs and proteins. Levels of MTOR, RPS6K, RPS6, and EIF4EBP1 mRNAs were not affected by treatment with any of the select nutrients. Similarly, expression of IFNT, NOS2, NOS3, and ODC1 mRNAs were not different. Interestingly, GCH1 mRNA levels increased in response to Arg treatment. Importantly, Arg, Leu, Gln, and glucose increased the abundance of phosphorylated MTOR, RPS6K, RPS6, and EIF4EBP1 proteins as well as NOS and ODC1 proteins, but only Arg increased the abundance of IFNT protein. These findings indicate that Arg, Leu, Gln, and glucose stimulate translation of mRNAs to increase synthesis of proteins through phosphorylation and activation of components of the MTOR Signaling pathway. Increases in abundance of IFNT protein (the pregnancy Recognition Signal), NOS2, NOS3 and GCH1 for conversion of Arg to nitric oxide, and ODC1 for synthesis of polyamines are all important for growth and development of the ovine conceptus during pregnancy.
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Discovery of candidate genes and pathways in the endometrium regulating ovine blastocyst growth and conceptus elongation
Physiological Genomics, 2009Co-Authors: M. Carey Satterfield, Fuller W Bazer, Gwonhwa Song, Kelli J. Kochan, Penny K. Riggs, Rebecca M. Simmons, Christine G. Elsik, David L. Adelson, Huaijun Zhou, Thomas E. SpencerAbstract:Establishment of pregnancy in ruminants requires blastocyst growth to form an elongated conceptus that produces interferon tau, the pregnancy Recognition Signal, and initiates implantation. Blastoc...
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Interferon Tau: A Novel Pregnancy Recognition Signal
American Journal of Reproductive Immunology, 1997Co-Authors: Fuller W Bazer, Thomas E. SpencerAbstract:PROBLEM: Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tau interferons (IFNτ) as the pregnancy Recognition Signal. How does it act? METHOD: Review of current data. RESULTS: IFNt acts on uterine epithelium to suppress transcription of the genes for estrogen receptor and oxytocin receptor. This blocks development of the uterine luteolytic mechanism and, therefore, release of luteolytic pulses of prostaglandin F 2α , but it has no effect on expression of the progesterone receptor. Maintenance of progesterone secretion by the corpus luteum ensures establishment and maintenance of pregnancy. Secretion of IFNτ on days 12-15 for sheep and days 14-17 for cows and goats is essential for pregnancy Recognition. CONCLUSION: We propose that IFNτ affects endometrial gene expression by activating the Jak/Stat pathway, which results in formation of the ISGF3α transcription factor complex. ISGF3α binds to interferon-stimulated response elements and activates transcription of interferon-responsive genes such as interferon regulatory factor-1 (IRF-1) which, in turn, activates expression of the negative-acting transcription factor IRF-2. Pregnancy (or intrauterine injection of roIFNτ) results in a transient increase in endometrial IRF-1 expression followed 36-48 hr later by a sustained increase in IRF-2. We propose that IRF-2, or an IFNτ-induced negative regulatory factor like IRF-2, suppresses expression of the estrogen receptor gene and directly or indirectly blocks expression of the gene for oxytocin receptor to abrogate the uterine luteolytic mechanism and ensure the establishment of pregnancy.
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τ-Interferon: Pregnancy Recognition Signal in Ruminants
Experimental Biology and Medicine, 1996Co-Authors: Thomas E. Spencer, Fuller W BazerAbstract:SummaryThe ovine uterus provides an excellent in vivo model system for the study of the cellular and molecular mechanisms of Type I IFN and steroid hormone regulation of hormone receptor gene expression in an epitheliomesenchymal organ. Future experiments will be directed toward determining the Signal transduction pathway activated by IFN-τ and mechanisms involved in regulation of gene expression. These experiments include (i) cloning the Type I IFN receptor found on the endometrial luminal and superficial glandular epithelium; (ii) eluciding the Signal transduction pathway activated by IFN-τ binding to the Type I IFN receptor; (iii) cloning and structural analysis of the ovine ER and OTR genes; (iv) determining mechanisms regulating transcription of the ovine ER and OTR genes, particularly those involving both IFN-τ and progesterone; (v) determining the role(s) of IFN-τ-induced proteins (e.g., Mx protein) in establishment of pregnancy; and (vi) investigating conceptus-endometrial and epithelial-stromal i...
Laurent Heutte - One of the best experts on this subject based on the ideXlab platform.
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Breast Cancer Histopathological Image Classification using Convolutional Neural Networks
International Joint Conference on Neural Networks (IJCNN 2016), 2016Co-Authors: Fabio A Spanhol, Luiz S. Oliveira, Cyril Petitjean, Laurent HeutteAbstract:The performance of most conventional classification systems relies on appropriate data representation and much of the efforts are dedicated to feature engineering, a difficult and time-consuming process that uses prior expert domain knowledge of the data to create useful features. On the other hand, deep learning can extract and organize the discriminative information from the data, not requiring the design of feature extractors by a domain expert. Convolutional Neural Networks (CNNs) are a particular type of deep, feedforward network that have gained attention from research community and industry, achieving empirical successes in tasks such as speech Recognition, Signal processing, object Recognition, natural language processing and transfer learning. In this paper, we conduct some preliminary ex- periments using the deep learning approach to classify breast can- cer histopathological images from BreaKHis, a publicly dataset available at http://web.inf.ufpr.br/vri/breast-cancer-database. We propose a method based on the extraction of image patches for training the CNN and the combination of these patches for final classification. This method aims to allow using the high- resolution histopathological images from BreaKHis as input to existing CNN, avoiding adaptations of themodel that can lead to a more complex and computationally costly architecture. The CNN performance is better when compared to previously reported results obtained by other machine learning models trained with hand-crafted textural descriptors. Finally, we also investigate the combination of different CNNs using simple fusion rules, achieving some improvement in Recognition rates.