CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis

Science.gov (United States)

Oh, Kyoung-Jin; Han, Hye-Sook; Kim, Min-Jung; Koo, Seung-Hoi

2013-01-01

Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed. [BMB Reports 2013; 46(12): 567-574] PMID:24238363

Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Park, Seong-Yeol; Bae, Young-Seuk, E-mail: ysbae@knu.ac.kr

2016-09-09

We previously showed that protein kinase CK2 downregulation mediates senescence through the reactive oxygen species (ROS)–p53–p21{sup Cip1/WAF1} pathway in various human cells. In the present study, we investigated whether the FoxO3a transcription factor is associated with ROS production during CK2 downregulation-induced senescence in human colon cancer HCT116 and breast cancer MCF-7 cells. FoxO3a overexpression suppressed ROS production and p53 stabilization induced by a CK2α knockdown. CK2α downregulation induced nuclear export of FoxO3a through stimulation of AKT-mediated phosphorylation of FoxO3a and decreased transcription of its target genes (Cu/ZnSOD, MnSOD, and catalase). In contrast, CK2α overexpression inhibited AKT-mediated FoxO3a phosphorylation. This resulted in nuclear accumulation of FoxO3a, and elevated expression of its target genes. Therefore, these data indicate for the first time that CK2 downregulation stimulates ROS generation by inhibiting FoxO3a during premature senescence in human colon and breast cancer cells. - Highlights: • FoxO3a overexpression inhibited ROS production mediated by CK2α knockdown. • CK2α downregulation induced nuclear export of FoxO3a via AKT activation. • CK2α downregulation reduced transcription of FoxO3a target genes including SOD. • CK2α upregulation elevated nuclear import and target gene expression of FoxO3a. • This study indicates that CK2 can modulate the intracellular ROS level via FoxO3a.

FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines

NARCIS (Netherlands)

Sunters, A.; Fernandez de Mattos, S.; Stahl, M.; Brosens, J.J.; Zoumpoulidou, G.; Saunders, C.A.; Coffer, P.J.; Medema, R.H.; Coombes, R.C.; Lam, E.W.-F.

2003-01-01

Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied the role of the FoxO transcription factors in determining cellular response to paclitaxel. Western blotting revealed that in a panel of nine breast cancer

FoxO3a transcriptional regulation of bim controls apoptosis in paclitaxel-treated breast cancer cell lines

NARCIS (Netherlands)

Sunters, A; de Mattos, SF; Stahl, M; Brosens, JJ; Zoumpoulidou, G; Saunders, CA; Coffer, PJ; Medema, RH; Coombes, RC; Lam, EWF

2003-01-01

Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied the role of the FoxO transcription factors in determining cellular response to paclitaxel. Western blotting revealed that in a panel of nine breast cancer

A Fork in the Path: Developing Therapeutic Inroads with FoxO Proteins

Directory of Open Access Journals (Sweden)

Kenneth Maiese

2009-01-01

Full Text Available Advances in clinical care for disorders involving any system of the body necessitates novel therapeutic strategies that can focus upon the modulation of cellular proliferation, metabolism, inflammation and longevity. In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. Furthermore, these transcription factors are closely integrated with several novel signal transduction pathways, such as erythropoietin and Wnt proteins, that may influence the ability of FoxOs to act as a “double-edge sword” to sometimes promote cell survival, but at other times lead to cell injury. Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.

Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells.

Science.gov (United States)

Park, Seong-Yeol; Bae, Young-Seuk

2016-09-09

We previously showed that protein kinase CK2 downregulation mediates senescence through the reactive oxygen species (ROS)-p53-p21(Cip1/WAF1) pathway in various human cells. In the present study, we investigated whether the FoxO3a transcription factor is associated with ROS production during CK2 downregulation-induced senescence in human colon cancer HCT116 and breast cancer MCF-7 cells. FoxO3a overexpression suppressed ROS production and p53 stabilization induced by a CK2α knockdown. CK2α downregulation induced nuclear export of FoxO3a through stimulation of AKT-mediated phosphorylation of FoxO3a and decreased transcription of its target genes (Cu/ZnSOD, MnSOD, and catalase). In contrast, CK2α overexpression inhibited AKT-mediated FoxO3a phosphorylation. This resulted in nuclear accumulation of FoxO3a, and elevated expression of its target genes. Therefore, these data indicate for the first time that CK2 downregulation stimulates ROS generation by inhibiting FoxO3a during premature senescence in human colon and breast cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

FoxO6 and PGC-1? form a regulatory loop in myogenic cells

OpenAIRE

Chung, Shih?Ying; Huang, Wei?Chieh; Su, Ching?Wen; Lee, Kuan?Wei; Chi, Hsiang?Cheng; Lin, Cheng?Tao; Chen, Szu-Tah; Huang, Kai?Min; Tsai, Mu?Shiun; Yu, Hui?Peng; Chen, Shen?Liang

2013-01-01

Transcription factors of the FoxO (forkhead box O) family regulate a wide range of cellular physiological processes, including metabolic adaptation and myogenic differentiation. The transcriptional activity of most FoxO members is inhibitory to myogenic differentiation and overexpression of FoxO1 inhibits the development of oxidative type?I fibres in?vivo. In this study, we found that FoxO6, the last discovered FoxO family member, is expressed ubiquitously in various tissues but with higher e...

Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.

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Fu, G; Peng, C

2011-09-15

Nodal, a member of the transforming growth factor-β superfamily, has been recently shown to suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in human epithelial ovarian cancer cells. However, the precise mechanisms underlying these events are not fully understood. In this study, we investigated the transcriptional regulation of CCNG2 by the Nodal signaling pathway. In ovarian cancer cells, overexpression of Nodal or its receptors, activin receptor-like kinase 7 (ALK7) or ALK4, resulted in an increase in the CCNG2 promoter activity. Several putative Forkhead box class O (FoxO)3a-binding sites are present in the human CCNG2 promoter and overexpression of FoxO3a enhanced the CCNG2 promoter activity. The functional FoxO3a-binding element (FBE) was mapped to a proximal region located between -398 and -380 bp (FBE1) through deletion and mutation analyses, as well as chromatin immunoprecipitation (IP) assay. Interestingly, mutation of the FBE1 not only abolished the effect of FoxO3a, but also blocked Nodal-induced CCNG2 transcription. Nodal stimulated FoxO3a mRNA and protein expression through the canonical Smad pathway and suppressed FoxO3a inactivation by inhibiting AKT activity. Silencing of FoxO3a using small interfering RNA significantly reduced the effect of Nodal on the CCNG2 promoter activity. On the other hand, overexpression of Smad2 and Smad3 enhanced the FoxO3a-induced CCNG2 promoter activity whereas knockdown of Smad4 blocked the activity of FoxO3a. Furthermore, IP assays revealed that FoxO3a formed complexes with Smad proteins and that Nodal enhanced the binding of FoxO3a to the CCNG2 promoter. Finally, silencing of FoxO3a reversed the inhibitory effect of Nodal on cell proliferation. Taken together, these findings demonstrated that Nodal signaling promotes CCNG2 transcription by upregulating FoxO3a expression, inhibiting FoxO3a phosphorylation and enhancing its synergistic interaction with Smads. These results also suggest

Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1

International Nuclear Information System (INIS)

Hatta, M.; Liu, F.; Cirillo, L.A.

2009-01-01

Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.

Forkhead box O transcription factors as possible mediators in the development of major depression.

Science.gov (United States)

Wang, Haitao; Quirion, Rémi; Little, Peter J; Cheng, Yufang; Feng, Zhong-Ping; Sun, Hong-Shuo; Xu, Jiangping; Zheng, Wenhua

2015-12-01

Forkhead box O (FoxO) transcription factors play important roles in cellular physiology and biology. Recent findings indicate that FoxOs are also involved in the development of major depressive disorder. Alterations in the upstream molecules of FoxOs, such as brain derived neurotrophic factor or protein kinase B, have been linked to depression. Antidepressants, such as imipramine and venlafaxine, modify the FoxOs phosphorylation. Furthermore, FoxOs could be regulated by serotonin and norepinephrine receptor signaling as well as the hypothalamic-pituitary-adrenal axis, all of which are involved in the pathogenesis of depression. FoxOs also regulate neuronal morphology, synaptogenesis and adult hippocampal neurogenesis, which are viewed as candidate mechanisms for the etiology of depression. In this review, we emphasize the possible roles of FoxOs during the development of depression and make some strategic recommendations for future research. We propose that FoxOs and its signaling pathways may constitute potential therapeutic targets in the treatment of depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin.

Directory of Open Access Journals (Sweden)

Christopher E Slagle

2011-05-01

Full Text Available Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.

FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase

Science.gov (United States)

Doan, Khanh V.; Kinyua, Ann W.; Yang, Dong Joo; Ko, Chang Mann; Moh, Sang Hyun; Shong, Ko Eun; Kim, Hail; Park, Sang-Kyu; Kim, Dong-Hoon; Kim, Inki; Paik, Ji-Hye; DePinho, Ronald A.; Yoon, Seul Gi; Kim, Il Yong; Seong, Je Kyung; Choi, Yun-Hee; Kim, Ki Woo

2016-01-01

Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KODAT) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KODAT mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis. PMID:27681312

FoxM1 is a general target for proteasome inhibitors.

Directory of Open Access Journals (Sweden)

Uppoor G Bhat

2009-08-01

Full Text Available Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties.

Forkhead-box transcription factors and their role in the immune system

NARCIS (Netherlands)

Coffer, PJ; Burgering, BMT

2004-01-01

It is more than a decade since the discovery of the first forkhead-box (FOX) transcription factor in the fruit fly Drosophila melanogaster. In the intervening time, there has been an explosion in the identification and characterization of members of this family of proteins. Importantly, in the past

Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.

Science.gov (United States)

Chen, Albert Tzong-Yang; Guo, Chunfang; Itani, Omar A; Budaitis, Breane G; Williams, Travis W; Hopkins, Christopher E; McEachin, Richard C; Pande, Manjusha; Grant, Ana R; Yoshina, Sawako; Mitani, Shohei; Hu, Patrick J

2015-10-01

FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental

Neuronal IFN-beta-induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1(+)Treg cells

DEFF Research Database (Denmark)

Liu, Yawei; Marin, Andrea; Ejlerskov, Patrick

2017-01-01

Neurons reprogramme encephalitogenic T cells (Tenc) to regulatory T cells (Tregs), either FoxP3(+)Tregs or FoxA1(+)Tregs. We reported previously that neuronal ability to generate FoxA1(+)Tregs was central to preventing neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Mice...... lacking interferon (IFN)-β were defective in generating FoxA1(+)Tregs in the brain. Here we show that lack of neuronal IFNβ signalling is associated with the absence of programme death ligand-1 (PDL1), which prevents their ability to reprogramme Tenc cells to FoxA1(+)Tregs. Passive transfer-EAE via IFNβ......-competent Tenc cells to mice lacking IFNβ and active induced-EAE in mice lacking its receptor, IFNAR, in the brain (Nes(Cre):Ifnar(fl/fl)) result in defective FoxA1(+)Tregs generation and aggravated neuroinflammation. IFNβ activates neuronal PI3K/Akt signalling and Akt binds to transcription factor FoxA1...

Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

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Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

2009-11-01

The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

Phylogenetic relationships of the Fox (Forkhead) gene family in the Bilateria

Science.gov (United States)

Mazet, Francoise; Yu, Jr Kai; Liberles, David A.; Holland, Linda Z.; Shimeld, Sebastian M.

2003-01-01

The Forkhead or Fox gene family encodes putative transcription factors. There are at least four Fox genes in yeast, 16 in Drosophila melanogaster (Dm) and 42 in humans. Recently, vertebrate Fox genes have been classified into 17 groups named FoxA to FoxQ. Here, we extend this analysis to invertebrates, using available sequences from D. melanogaster, Anopheles gambiae (Ag), Caenorhabditis elegans (Ce), the sea squirt Ciona intestinalis (Ci) and amphioxus Branchiostoma floridae (Bf), from which we also cloned several Fox genes. Phylogenetic analyses lend support to the previous overall subclassification of vertebrate genes, but suggest that four subclasses (FoxJ, L, N and Q) could be further subdivided to reflect their relationships to invertebrate genes. We were unable to identify orthologs of Fox subclasses E, H, I, J, M and Q1 in D. melanogaster, A. gambiae or C. elegans, suggesting either considerable loss in ecdysozoans or the evolution of these subclasses in the deuterostome lineage. Our analyses suggest that the common ancestor of protostomes and deuterostomes had a minimum complement of 14 Fox genes.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

Science.gov (United States)

Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

2013-01-01

SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

Similarities between the Epstein-Barr Virus (EBV) Nuclear Protein EBNA1 and the Pioneer Transcription Factor FoxA: Is EBNA1 a “Bookmarking” Oncoprotein that Alters the Host Cell Epigenotype?

Science.gov (United States)

Niller, Hans Helmut; Minarovits, Janos

2012-01-01

EBNA1, a nuclear protein expressed in all EBV-associated neoplasms is indispensable for the maintenance of the viral episomes in latently infected cells. EBNA1 may induce genetic alterations by upregulating cellular recombinases, production of reactive oxygen species (ROS) and affecting p53 levels and function. All these changes may contribute to tumorigenesis. In this overview we focus, however, on the epigenetic alterations elicited by EBNA1 by drawing a parallel between EBNA1 and the FoxA family of pioneer transcription factors. Both EBNA1 and FoxA induce local DNA demethylation, nucleosome destabilization and bind to mitotic chromosomes. Local DNA demethylation and nucleosome rearrangement mark active promoters and enhancers. In addition, EBNA1 and FoxA, when associated with mitotic chromatin may “bookmark” active genes and ensure their reactivation in postmitotic cells (epigenetic memory). We speculate that DNA looping induced by EBNA1-EBNA1 interactions may reorganize the cellular genome. Such chromatin loops, sustained in mitotic chromatin similarly to the long-distance interactions mediated by the insulator protein CTCF, may also mediate the epigenetic inheritance of gene expression patterns. We suggest that EBNA1 has the potential to induce patho-epigenetic alterations contributing to tumorigenesis. PMID:25436603

AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

OpenAIRE

Zhao, Shanchao; Bao, Jiming; Song, Xianlu

2016-01-01

Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% c...

Accelerated FoxP2 evolution in echolocating bats.

Directory of Open Access Journals (Sweden)

Gang Li

Full Text Available FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination.

SCP4 Promotes gluconeogenesis through Fox01/3a dephosphorylation

Science.gov (United States)

FoxO1 and FoxO3a (collectively FoxO1/3a) proteins regulate a wide array of cellular processes, including hepatic gluconeogenesis. Phosphorylation of FoxO1/3a is a key event that determines its subcellular location and transcriptional activity. During glucose synthesis, the activity of FoxO1/3a is ne...

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

Science.gov (United States)

Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

2016-01-01

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

Quantification of transcription factor-DNA binding affinity in a living cell.

Science.gov (United States)

Belikov, Sergey; Berg, Otto G; Wrange, Örjan

2016-04-20

The apparent dissociation constant (Kd) for specific binding of glucocorticoid receptor (GR) and androgen receptor (AR) to DNA was determined in vivo in Xenopus oocytes. The total nuclear receptor concentration was quantified as specifically retained [(3)H]-hormone in manually isolated oocyte nuclei. DNA was introduced by nuclear microinjection of single stranded phagemid DNA, chromatin is then formed during second strand synthesis. The fraction of DNA sites occupied by the expressed receptor was determined by dimethylsulphate in vivo footprinting and used for calculation of the receptor-DNA binding affinity. The forkhead transcription factor FoxA1 enhanced the DNA binding by GR with an apparent Kd of ∼1 μM and dramatically stimulated DNA binding by AR with an apparent Kd of ∼0.13 μM at a composite androgen responsive DNA element containing one FoxA1 binding site and one palindromic hormone receptor binding site known to bind one receptor homodimer. FoxA1 exerted a weak constitutive- and strongly cooperative DNA binding together with AR but had a less prominent effect with GR, the difference reflecting the licensing function of FoxA1 at this androgen responsive DNA element. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection

Science.gov (United States)

Hosein, Shazia; Rodríguez-Cortés, Alhelí; Blake, Damer P.; Allenspach, Karin; Alberola, Jordi; Solano-Gallego, Laia

2015-01-01

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in

FoxO and stress responses in the cnidarian Hydra vulgaris.

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Diane Bridge

2010-07-01

Full Text Available In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms.We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases.These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians and raise the possibility that FoxO is involved in stress responses of other cnidarian species, including corals.

Phenotypically non-suppressive cells predominate among FoxP3-positive cells in oral lichen planus.

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Schreurs, Olav; Karatsaidis, Andreas; Schenck, Karl

2016-11-01

Oral lichen planus (OLP) is a common T-cell-dominated oral chronic inflammatory disease occurring in periods of remission, quiescence, activity with pronounced inflammation, and acute ulceration. Cell infiltrates in OLP contain varying numbers of CD4 + T cells expressing the transcription factor FoxP3. FoxP3 + CD4 + T cells are, however, a heterogeneous cell population containing suppressive and non-suppressive cells, and their distribution in infiltrates from OLP is unknown. Biopsies were taken from normal oral mucosa (n = 8) and OLP lesions (n = 19), and a set of in situ methods for the determination of the functional phenotype of FoxP3 + CD4 + T cells was applied. Numbers of FoxP3 + CD4 + T cells were highest in the atrophic form of the disease, yet low in the ulcerative form. The main FoxP3 + CD4 + T-cell population observed was FoxP3 + CD45RA - CD25 + CD45RO + and CD15s - , a phenotype delineating a non-suppressive subset. Numbers of cells with an actively suppressing phenotype (FoxP3 + CD45RA - CD25 + CD45RO + and CD15s + ) were, however, about twice as high in reticular lesions as compared with the atrophic form. Many FoxP3 + CD4 + T cells expressed T-bet, the hallmark transcription factor for IFN-γ-producing T cells, indicating that they may enhance immune and inflammatory responses rather than suppress them. The absence of actively suppressing FoxP3 + CD4 + T cells may in part explain why OLP is a remarkably persisting condition, in spite of the presence of substantially high numbers of FoxP3 + CD4 + T cells. The findings emphasize that it is crucial to examine not only numbers but also functional phenotype of FoxP3 + CD4 + T cells in human tissues. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Trends in anecdotal fox sightings in Tasmania accounted for by psychological factors.

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Marks, Clive A; Clark, Malcolm; Obendorf, David; Hall, Graham P; Soares, Inês; Pereira, Filipe

2017-12-01

There has been little evaluation of anecdotal sightings as a means to confirm new incursions of invasive species. This paper explores the potential for equivocal information communicated by the media to account for patterns of anecdotal reports. In 2001, it was widely reported that red foxes (Vulpes vulpes) had been deliberately released in the island state of Tasmania (Australia), although this claim was later revealed to be baseless. Regardless, by 2013 a total of 3153 anecdotal fox sightings had been reported by members of the public, which implied their distribution was wide. For each month in 2001-2003, we defined a monthly media index (MMI) of fox-related media coverage, an index of their relative seasonal abundance (abundance), and a factor denoting claims of fox evidence (claimed evidence) regardless of its evidentiary quality. We fitted a generalized linear model with Poisson error for monthly totals of anecdotal sightings with factors of year and claimed evidence and covariates of MMI, abundance, and hours of darkness. The collective effect of psychological factors (MMI, claimed evidence, and year) relative to biophysical factors (photoperiod and abundance) was highly significant (χ 2 = 122.1, df = 6, p fox media from 2001 to 2010 was strongly associated with the yearly tally of anecdotal sightings (p = 0.018). The odds ratio of sightings ranked as reliable by the fox eradication program in any year decreased exponentially at a rate of 0.00643 as the total number of sightings increased (p < 0.0001) and was indicative of an observer-expectancy bias. Our results suggest anecdotal sightings are highly susceptible to cognitive biases and when used to qualify and quantify species presence can contribute to flawed risk assessments. © 2017 Society for Conservation Biology.

FoxA1 as a lineage-specific oncogene in luminal type breast cancer

International Nuclear Information System (INIS)

Yamaguchi, Noritaka; Ito, Emi; Azuma, Sakura; Honma, Reiko; Yanagisawa, Yuka; Nishikawa, Akira; Kawamura, Mika; Imai, Jun-ichi

2008-01-01

The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells

Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation.

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Chen, Albert Tzong-Yang; Guo, Chunfang; Dumas, Kathleen J; Ashrafi, Kaveh; Hu, Patrick J

2013-10-01

The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Expression of Fox genes in the cephalochordate Branchiostoma lanceolatum

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Daniel eAldea

2015-07-01

Full Text Available Forkhead box (Fox genes code for transcription factors that play important roles in different biological processes. They are found in a wide variety of organisms and appeared in unicellular eukaryotes. In metazoans, the gene family includes many members that can be subdivided into 24 classes. Cephalochordates are key organisms to understand the functional evolution of gene families in the chordate lineage due to their phylogenetic position as an early divergent chordate, their simple anatomy and genome structure. In the genome of the cephalochordate amphioxus Branchiostoma floridae, 32 Fox genes were identified, with at least one member for each of the classes that were present in the ancestor of bilaterians. In this work we describe the expression pattern of 13 of these genes during the embryonic development of the Mediterranean amphioxus, Branchiostoma lanceolatum. We found that FoxK and FoxM genes present an ubiquitous expression while all the others show specific expression patterns restricted to diverse embryonic territories. Many of these expression patterns are conserved with vertebrates, suggesting that the main functions of Fox genes in chordates were present in their common ancestor.

SCP4 Promotes Gluconeogenesis Through FoxO1/3a Dephosphorylation.

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Cao, Jin; Yu, Yi; Zhang, Zhengmao; Chen, Xi; Hu, Zhaoyong; Tong, Qiang; Chang, Jiang; Feng, Xin-Hua; Lin, Xia

2018-01-01

FoxO1 and FoxO3a (collectively FoxO1/3a) proteins regulate a wide array of cellular processes, including hepatic gluconeogenesis. Phosphorylation of FoxO1/3a is a key event that determines its subcellular location and transcriptional activity. During glucose synthesis, the activity of FoxO1/3a is negatively regulated by Akt-mediated phosphorylation, which leads to the cytoplasmic retention of FoxO1/3a. However, the nuclear phosphatase that directly regulates FoxO1/3a remains to be identified. In this study, we discovered a nuclear phosphatase, SCP4/CTDSPL2 (SCP4), that dephosphorylated FoxO1/3a and promoted FoxO1/3a transcription activity. We found that SCP4 enhanced the transcription of FoxO1/3a target genes encoding PEPCK1 and G6PC, key enzymes in hepatic gluconeogenesis. Ectopic expression of SCP4 increased, while knockdown of SCP4 inhibited, glucose production. Moreover, we demonstrated that gene ablation of SCP4 led to hypoglycemia in neonatal mice. Consistent with the positive role of SCP4 in gluconeogenesis, expression of SCP4 was regulated under pathophysiological conditions. SCP4 expression was induced by glucose deprivation in vitro and in vivo and was elevated in obese mice caused by genetic (A vy ) and dietary (high-fat) changes. Thus, our findings provided experimental evidence that SCP4 regulates hepatic gluconeogenesis and could serve as a potential target for the prevention and treatment of diet-induced glucose intolerance and type 2 diabetes. © 2017 by the American Diabetes Association.

Forkhead box transcription factors in embryonic heart development and congenital heart disease.

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Zhu, Hong

2016-01-01

Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic Regulation of FoxA1 by Steroid Receptors | Center for Cancer Research

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The estrogen receptor (ER) is a key regulator in breast cancer initiation and progression. A widely discussed model proposes that forkhead box protein A1 (FoxA1) acts as a pioneer factor in cancer by binding and penetrating closed chromatin to allow access by transcription factors (TFs), including ER.

Linking Alzheimer's disease to insulin resistance: the FoxO response to oxidative stress.

Science.gov (United States)

Manolopoulos, K N; Klotz, L-O; Korsten, P; Bornstein, S R; Barthel, A

2010-11-01

Oxidative stress is an important determinant not only in the pathogenesis of Alzheimer's disease (AD), but also in insulin resistance (InsRes) and diabetic complications. Forkhead box class O (FoxO) transcription factors are involved in both insulin action and the cellular response to oxidative stress, thereby providing a potential integrative link between AD and InsRes. For example, the expression of intra- and extracellular antioxidant enzymes, such as manganese-superoxide dismutase and selenoprotein P, is regulated by FoxO proteins, as is the expression of important hepatic enzymes of gluconeogenesis. Here, we review the molecular mechanisms involved in the pathogenesis of AD and InsRes and discuss the function of FoxO proteins in these processes. Both InsRes and oxidative stress may promote the transcriptional activity of FoxO proteins, resulting in hyperglycaemia and a further increased production of reactive oxygen species (ROS). The consecutive activation of c-Jun N-terminal kinases and inhibition of Wingless (Wnt) signalling may result in the formation of β-amyloid plaques and τ protein phosphorylation. Wnt inhibition may also result in a sustained activation of FoxO proteins with induction of apoptosis and neuronal loss, thereby completing a vicious circle from oxidative stress, InsRes and hyperglycaemia back to the formation of ROS and consecutive neurodegeneration. In view of their central function in this model, FoxO proteins may provide a potential molecular target for the treatment of both InsRes and AD.

USP7 Attenuates Hepatic Gluconeogenesis Through Modulation of FoxO1 Gene Promoter Occupancy

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Hall, Jessica A.; Tabata, Mitsuhisa; Rodgers, Joseph T.

2014-01-01

Hepatic forkhead protein FoxO1 is a key component of systemic glucose homeostasis via its ability to regulate the transcription of rate-limiting enzymes in gluconeogenesis. Important in the regulation of FoxO1 transcriptional activity are the modifying/demodifying enzymes that lead to posttranslational modification. Here, we demonstrate the functional interaction and regulation of FoxO1 by herpesvirus-associated ubiquitin-specific protease 7 (USP7; also known as herpesvirus-associated ubiquitin-specific protease, HAUSP), a deubiquitinating enzyme. We show that USP7-mediated mono-deubiquitination of FoxO1 results in suppression of FoxO1 transcriptional activity through decreased FoxO1 occupancy on the promoters of gluconeogenic genes. Knockdown of USP7 in primary hepatocytes leads to increased expression of FoxO1-target gluconeogenic genes and elevated glucose production. Consistent with this, USP7 gain-of-function suppresses the fasting/cAMP-induced activation of gluconeogenic genes in hepatocyte cells and in mouse liver, resulting in decreased hepatic glucose production. Notably, we show that the effects of USP7 on hepatic glucose metabolism depend on FoxO1. Together, these results place FoxO1 under the intimate regulation of deubiquitination and glucose metabolic control with important implication in diseases such as diabetes. PMID:24694308

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

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Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

2013-05-01

FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

Roles of Forkhead-box Transcription Factors in Controlling Development, Pathogenicity, and Stress Response in Magnaporthe oryzae

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Jaejin Park

2014-06-01

Full Text Available Although multiple transcription factors (TFs have been characterized via mutagenesis to understand their roles in controlling pathogenicity and infection-related development in Magnaporthe oryzae, the causal agent of rice blast, if and how forkhead-box (FOX TFs contribute to these processes remain to be characterized. Four putative FOX TF genes were identified in the genome of M. oryzae, and phylogenetic analysis suggested that two of them (MoFKH1 and MoHCM1 correspond to Ascomycota-specific members of the FOX TF family while the others (MoFOX1 and MoFOX2 are Pezizomycotina-specific members. Deletion of MoFKH1 (ΔMofkh1 resulted in reduced mycelial growth and conidial germination, abnormal septation and stress response, and reduced virulence. Similarly, ΔMohcm1 exhibited reduced mycelial growth and conidial germination. Conidia of ΔMofkh1 and ΔMohcm1 were more sensitive to one or both of the cell cycle inhibitors hydroxyurea and benomyl, suggesting their role in cell cycle control. On the other hand, loss of MoFOX1 (ΔMofox1 did not show any noticeable changes in development, pathogenicity, and stress response. Deletion of MoFOX2 was not successful even after repeated attempts. Taken together, these results suggested that MoFKH1 and Mo-HCM1 are important in fungal development and that MoFKH1 is further implicated in pathogenicity and stress response in M. oryzae.

FoxO1 gain of function in the pancreas causes glucose intolerance, polycystic pancreas, and islet hypervascularization.

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Osamu Kikuchi

Full Text Available Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice. However, it is still unclear whether FoxO1 dysregulation in the pancreas could be the cause of diabetes. To test this hypothesis, we generated transgenic mice overexpressing constitutively active FoxO1 specifically in the pancreas (TG. TG mice had impaired glucose tolerance and some of them indeed developed diabetes due to the reduction of β cell mass, which is associated with decreased Pdx1 and MafA in β cells. We also observed increased proliferation of pancreatic duct epithelial cells in TG mice and some mice developed a polycystic pancreas as they aged. Furthermore, TG mice exhibited islet hypervascularities due to increased VEGF-A expression in β cells. We found FoxO1 binds to the VEGF-A promoter and regulates VEGF-A transcription in β cells. We propose that dysregulation of FoxO1 activity in the pancreas could account for the development of diabetes and pancreatic cysts.

FoxO1 Plays an Important Role in Regulating ?-Cell Compensation for Insulin Resistance in Male Mice

OpenAIRE

Zhang, Ting; Kim, Dae Hyun; Xiao, Xiangwei; Lee, Sojin; Gong, Zhenwei; Muzumdar, Radhika; Calabuig-Navarro, Virtu; Yamauchi, Jun; Harashima, Hideyoshi; Wang, Rennian; Bottino, Rita; Alvarez-Perez, Juan Carlos; Garcia-Oca?a, Adolfo; Gittes, George; Dong, H. Henry

2016-01-01

?-Cell compensation is an essential mechanism by which ?-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of ?-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of ?-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in ?-cell compensation in mice under physiological and pathological conditions. FoxO1 is a key transcription factor that...

CD36-dependent Regulation of Muscle FoxO1 and PDK4 in the PPARδ/β-mediated Adaptation to Metabolic Stress*

OpenAIRE

Nahlé, Zaher; Hsieh, Michael; Pietka, Terri; Coburn, Chris T.; Grimaldi, Paul A.; Zhang, Michael Q.; Das, Debopriya; Abumrad, Nada A.

2008-01-01

The transcription factor FoxO1 contributes to the metabolic adaptation to fasting by suppressing muscle oxidation of glucose, sparing it for glucose-dependent tissues. Previously, we reported that FoxO1 activation in C2C12 muscle cells recruits the fatty acid translocase CD36 to the plasma membrane and increases fatty acid uptake and oxidation. This, together with FoxO1 induction of lipoprotein lipase, would promote the reliance on fatty acid utilization characteristic of the fasted muscle. H...

Platinum coat color in red fox (Vulpes vulpes) is caused by a mutation in an autosomal copy of KIT.

Science.gov (United States)

Johnson, J L; Kozysa, A; Kharlamova, A V; Gulevich, R G; Perelman, P L; Fong, H W F; Vladimirova, A V; Oskina, I N; Trut, L N; Kukekova, A V

2015-04-01

The red fox (Vulpes vulpes) demonstrates a variety of coat colors including platinum, a common phenotype maintained in farm-bred fox populations. Foxes heterozygous for the platinum allele have a light silver coat and extensive white spotting, whereas homozygosity is embryonic lethal. Two KIT transcripts were identified in skin cDNA from platinum foxes. The long transcript was identical to the KIT transcript of silver foxes, whereas the short transcript, which lacks exon 17, was specific to platinum. The KIT gene has several copies in the fox genome: an autosomal copy on chromosome 2 and additional copies on the B chromosomes. To identify the platinum-specific KIT sequence, the genomes of one platinum and one silver fox were sequenced. A single nucleotide polymorphism (SNP) was identified at the first nucleotide of KIT intron 17 in the platinum fox. In platinum foxes, the A allele of the SNP disrupts the donor splice site and causes exon 17, which is part of a segment that encodes a conserved tyrosine kinase domain, to be skipped. Complete cosegregation of the A allele with the platinum phenotype was confirmed by linkage mapping (LOD 25.59). All genotyped farm-bred platinum foxes from Russia and the US were heterozygous for the SNP (A/G), whereas foxes with different coat colors were homozygous for the G allele. Identification of the platinum mutation suggests that other fox white-spotting phenotypes, which are allelic to platinum, would also be caused by mutations in the KIT gene. © 2015 Stichting International Foundation for Animal Genetics.

The ThPOK transcription factor differentially affects the development and function of self-specific CD8(+) T cells and regulatory CD4(+) T cells.

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Twu, Yuh-Ching; Teh, Hung-Sia

2014-03-01

The zinc finger transcription factor ThPOK plays a crucial role in CD4 T-cell development and CD4/CD8 lineage decision. In ThPOK-deficient mice, developing T cells expressing MHC class II-restricted T-cell receptors are redirected into the CD8 T-cell lineage. In this study, we investigated whether the ThPOK transgene affected the development and function of two additional types of T cells, namely self-specific CD8 T cells and CD4(+) FoxP3(+) T regulatory cells. Self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11 and proliferation in response to either IL-2 or IL-15. The ThPOK transgene converted these self-specific CD8 T cells into CD4 T cells. The converted CD4(+) T cells are no longer self-reactive, lose the characteristics of self-specific CD8 T cells, acquire the properties of conventional CD4 T cells and survive poorly in peripheral lymphoid organs. By contrast, the ThPOK transgene promoted the development of CD4(+) FoxP3(+) regulatory T cells resulting in an increased recovery of CD4(+) FoxP3(+) regulatory T cells that expressed higher transforming growth factor-β-dependent suppressor activity. These studies indicate that the ThPOK transcription factor differentially affects the development and function of self-specific CD8 T cells and CD4(+) FoxP3(+) regulatory T cells. © 2013 John Wiley & Sons Ltd.

Function of the PHA-4/FOXA transcription factor during C. elegans post-embryonic development

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Chen Di

2008-02-01

Full Text Available Abstract Background pha-4 encodes a forkhead box (FOX A transcription factor serving as the C. elegans pharynx organ identity factor during embryogenesis. Using Serial Analysis of Gene Expression (SAGE, comparison of gene expression profiles between growing stages animals and long-lived, developmentally diapaused dauer larvae revealed that pha-4 transcription is increased in the dauer stage. Results Knocking down pha-4 expression by RNAi during post-embryonic development showed that PHA-4 is essential for dauer recovery, gonad and vulva development. daf-16, which encodes a FOXO transcription factor regulated by insulin/IGF-1 signaling, shows overlapping expression patterns and a loss-of-function post-embryonic phenotype similar to that of pha-4 during dauer recovery. pha-4 RNAi and daf-16 mutations have additive effects on dauer recovery, suggesting these two regulators may function in parallel pathways. Gene expression studies using RT-PCR and GFP reporters showed that pha-4 transcription is elevated under starvation, and a conserved forkhead transcription factor binding site in the second intron of pha-4 is important for the neuronal expression. The vulval transcription of lag-2, which encodes a ligand for the LIN-12/Notch lateral signaling pathway, is inhibited by pha-4 RNAi, indicating that LAG-2 functions downstream of PHA-4 in vulva development. Conclusion Analysis of PHA-4 during post-embryonic development revealed previously unsuspected functions for this important transcriptional regulator in dauer recovery, and may help explain the network of transcriptional control integrating organogenesis with the decision between growth and developmental arrest at the dauer entry and exit stages.

Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose metabolism through downregulation of gluconeogenesis and upregulation of glycolysis.

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Xiwen Xiong

Full Text Available Forkhead transcription factors FoxO1/3/4 have pleiotrophic functions including anti-oxidative stress and metabolism. With regard to glucose metabolism, most studies have been focused on FoxO1. To further investigate their hepatic functions, we generated liver-specific FoxO1/3/4 knockout mice (LTKO and examined their collective impacts on glucose homeostasis under physiological and pathological conditions. As compared to wild-type mice, LTKO mice had lower blood glucose levels under both fasting and non-fasting conditions and they manifested better glucose and pyruvate tolerance on regular chow diet. After challenged by a high-fat diet, wild-type mice developed type 2 diabetes, but LTKO mice remained euglycemic and insulin-sensitive. To understand the underlying mechanisms, we examined the roles of SIRT6 (Sirtuin 6 and Gck (glucokinase in the FoxO-mediated glucose metabolism. Interestingly, ectopic expression of SIRT6 in the liver only reduced gluconeogenesis in wild-type but not LTKO mice whereas knockdown of Gck caused glucose intolerance in both wild-type and LTKO mice. The data suggest that both decreased gluconeogenesis and increased glycolysis may contribute to the overall glucose phenotype in the LTKO mice. Collectively, FoxO1/3/4 transcription factors play important roles in hepatic glucose homeostasis.

Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

DEFF Research Database (Denmark)

Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

2014-01-01

Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

Effects of FoxO1 on podocyte injury in diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Guo, Feng; Zhang, Yuanyuan; Wang, Qingzhu; Ren, Lei; Zhou, Yingni [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Ma, Xiaojun [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wu, Lina [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Qin, Guijun, E-mail: hyqingj@zzu.edu.cn [Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China)

2015-10-16

Objective: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Results: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Conclusions: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. - Highlights: • The structures and functions of podocytes were impaired in STZ-induced diabetic rats. • Constitutively active FoxO1 ameliorates structure injury and preserves function of podocytes in diabetic rats. • FoxO1 may alleviate the pathological changes associated with diabetic nephropathy.

Effects of FoxO1 on podocyte injury in diabetic rats

International Nuclear Information System (INIS)

Guo, Feng; Zhang, Yuanyuan; Wang, Qingzhu; Ren, Lei; Zhou, Yingni; Ma, Xiaojun; Wu, Lina; Qin, Guijun

2015-01-01

Objective: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. Methods: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. Results: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. Conclusions: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. - Highlights: • The structures and functions of podocytes were impaired in STZ-induced diabetic rats. • Constitutively active FoxO1 ameliorates structure injury and preserves function of podocytes in diabetic rats. • FoxO1 may alleviate the pathological changes associated with diabetic nephropathy.

The Drosophila FoxA ortholog Fork head regulates growth and gene expression downstream of Target of rapamycin.

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Margret H Bülow

2010-12-01

Full Text Available Forkhead transcription factors of the FoxO subfamily regulate gene expression programs downstream of the insulin signaling network. It is less clear which proteins mediate transcriptional control exerted by Target of rapamycin (TOR signaling, but recent studies in nematodes suggest a role for FoxA transcription factors downstream of TOR. In this study we present evidence that outlines a similar connection in Drosophila, in which the FoxA protein Fork head (FKH regulates cellular and organismal size downstream of TOR. We find that ectopic expression and targeted knockdown of FKH in larval tissues elicits different size phenotypes depending on nutrient state and TOR signaling levels. FKH overexpression has a negative effect on growth under fed conditions, and this phenotype is not further exacerbated by inhibition of TOR via rapamycin feeding. Under conditions of starvation or low TOR signaling levels, knockdown of FKH attenuates the size reduction associated with these conditions. Subcellular localization of endogenous FKH protein is shifted from predominantly cytoplasmic on a high-protein diet to a pronounced nuclear accumulation in animals with reduced levels of TOR or fed with rapamycin. Two putative FKH target genes, CG6770 and cabut, are transcriptionally induced by rapamycin or FKH expression, and silenced by FKH knockdown. Induction of both target genes in heterozygous TOR mutant animals is suppressed by mutations in fkh. Furthermore, TOR signaling levels and FKH impact on transcription of the dFOXO target gene d4E-BP, implying a point of crosstalk with the insulin pathway. In summary, our observations show that an alteration of FKH levels has an effect on cellular and organismal size, and that FKH function is required for the growth inhibition and target gene induction caused by low TOR signaling levels.

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb.

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Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L

2017-01-17

FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Redox-sensitive up-regulation of eNOS by purple grape juice in endothelial cells: role of PI3-kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a.

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Mahmoud Alhosin

Full Text Available The vascular protective effect of grape-derived polyphenols has been attributable, in part, to their direct action on blood vessels by stimulating the endothelial formation of nitric oxide (NO. The aim of the present study was to determine whether Concord grape juice (CGJ, which contains high levels of polyphenols, stimulates the expression of endothelial NO synthase (eNOS in porcine coronary artery endothelial cells and, if so, to determine the signaling pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein levels and this effect is associated with an increased formation of NO in endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated with an increased eNOS mRNA stability and inhibited by antioxidants such as MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3-kinase, SB 203580 (an inhibitor of p38 MAPK, and SP 600125 (an inhibitor of JNK. Moreover, CGJ induced the formation of reactive oxygen species (ROS in endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1 and FoxO3a, which regulate negatively eNOS expression, and this effect is prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover, chromatin immunoprecipitation assay indicated that the FoxO3a protein is associated with the eNOS promoter in control cells and that CGJ induced its dissociation. Thus, the present study indicates that CGJ up-regulates the expression of eNOS mRNA and protein leading to an increased formation of NO in endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression of the eNOS gene.

Missed, Not Missing: Phylogenomic Evidence for the Existence of Avian FoxP3.

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Michael P Denyer

Full Text Available The Forkhead box transcription factor FoxP3 is pivotal to the development and function of regulatory T cells (Tregs, which make a major contribution to peripheral tolerance. FoxP3 is believed to perform a regulatory role in all the vertebrate species in which it has been detected. The prevailing view is that FoxP3 is absent in birds and that avian Tregs rely on alternative developmental and suppressive pathways. Prompted by the automated annotation of foxp3 in the ground tit (Parus humilis genome, we have questioned this assumption. Our analysis of all available avian genomes has revealed that the foxp3 locus is missing, incomplete or of poor quality in the relevant genomic assemblies for nearly all avian species. Nevertheless, in two species, the peregrine falcon (Falco peregrinus and the saker falcon (F. cherrug, there is compelling evidence for the existence of exons showing synteny with foxp3 in the ground tit. A broader phylogenomic analysis has shown that FoxP3 sequences from these three species are similar to crocodilian sequences, the closest living relatives of birds. In both birds and crocodilians, we have also identified a highly proline-enriched region at the N terminus of FoxP3, a region previously identified only in mammals.

FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol.

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Ganjam, Goutham Kumar; Dimova, Elitsa Y; Unterman, Terry G; Kietzmann, Thomas

2009-11-06

Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.

FoxO3a Serves as a Biomarker of Oxidative Stress in Human Lens Epithelial Cells under Conditions of Hyperglycemia.

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Ilangovan Raju

Full Text Available Forkhead box 'O' transcription factors (FoxOs are implicated in the pathogenesis of type2 diabetes and other metabolic diseases. Abnormal activity of FoxOs was reported in the glucose and insulin metabolism. Expression of FoxO proteins was reported in ocular tissues; however their function under hyperglycemic conditions was not examined.Human lens epithelial cell line was used to study the function of FoxO proteins. Immunofluorescence, flow cytometry and Western blotting were employed to detect the FoxO proteins under the conditions of hyperglycemia.In this study we examined the role of FoxO3a in hyperglycemia-induced oxidative stress in human lens epithelial cells. FoxO3a protein expression was elevated in a dose- and time-dependent fashion after high glucose treatment. Anti-oxidant defense mechanisms of the lens epithelial cells were diminished as evidenced from loss of mitochondrial membrane integrity and lowered MnSOD after 72 h treatment with high glucose. Taken together, FoxO3a acts as a sensitive indicator of oxidative stress and cell homeostasis in human lens epithelial cells during diabetic conditions.FoxO3a is an early stress response protein to glucose toxicity in diabetic conditions.

Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid.

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Kinoshita, Asako; Locher, Lena; Tienken, Reka; Meyer, Ulrich; Dänicke, Sven; Rehage, Jürgen; Huber, Korinna

2016-01-01

Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively). Cows received 0 (LC-CON and HC-CON) or 24 (LC-NA and HC-NA) g/d nicotinic acid with high (HC) or low (LC) concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation) relative to expected calving date (d-42) to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1) and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1) were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at Pdairy cows in early lactation.

FoxO1 and HNF-4 Are Involved in Regulation of Hepatic Glucokinase Gene Expression by Resveratrol*

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Ganjam, Goutham Kumar; Dimova, Elitsa Y.; Unterman, Terry G.; Kietzmann, Thomas

2009-01-01

Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol. PMID:19740748

Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

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Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

2016-07-26

PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.

Inactivation of the forkhead transcription factor FoxO3 is essential for PKB-mediated survival of hematopoietic progenitor cells by kit ligand

DEFF Research Database (Denmark)

Engström, Maria; Karlsson, Richard; Jönsson, Jan-Ingvar

2003-01-01

OBJECTIVE: Kit ligand (KL) is a major survival factor for hematopoietic stem cells. Although anti-apoptotic bcl-2 family members are expressed in these cells, the survival effects by KL appear to involve other mechanisms. Survival signals can also be elicited by the activation of phosphatidylinos......OBJECTIVE: Kit ligand (KL) is a major survival factor for hematopoietic stem cells. Although anti-apoptotic bcl-2 family members are expressed in these cells, the survival effects by KL appear to involve other mechanisms. Survival signals can also be elicited by the activation......, immunofluorescence, and subcellular fractionation, we analyzed the effects of KL on PKB and different forkhead family members in two factor-dependent cell lines, FDCP-mix and FDC-P1, as well as primary mouse bone marrow-derived Lin(-) progenitors. Forced overexpression of triple mutated form of FoxO3 by retroviral...

Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

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E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.

Science.gov (United States)

Heglind, Mikael; Cederberg, Anna; Aquino, Jorge; Lucas, Guilherme; Ernfors, Patrik; Enerbäck, Sven

2005-07-01

To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

FoxO6 Integrates Insulin Signaling With Gluconeogenesis in the Liver

Science.gov (United States)

Kim, Dae Hyun; Perdomo, German; Zhang, Ting; Slusher, Sandra; Lee, Sojin; Phillips, Brett E.; Fan, Yong; Giannoukakis, Nick; Gramignoli, Roberto; Strom, Stephen; Ringquist, Steven; Dong, H. Henry

2011-01-01

OBJECTIVE Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND METHODS We characterized FoxO6 in glucose metabolism in cultured hepatocytes and in rodent models of dietary obesity, insulin resistance, or insulin-deficient diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in genetically modified mice with FoxO6 gain- versus loss-of-function and in diabetic db/db mice with selective FoxO6 ablation in the liver. RESULTS FoxO6 integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6 activity in the liver augments gluconeogenesis, raising fasting blood glucose levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin-resistant liver, accounting for its unbridled activity in promoting gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice. CONCLUSIONS Our data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes. PMID:21940782

WRKY transcription factors

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Bakshi, Madhunita; Oelmüller, Ralf

2014-01-01

WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

Factors Affecting Home Ranges of Red Foxes in Ikh Nart Nature Reserve, Mongolia

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Tserendorj Munkhzul

2012-12-01

Full Text Available Changes in red fox home range size in relation to environmental and intrinsic factors were studied using radio-telemetry during 2006–2008 in Ikh Nart Nature Reserve, southeastern Mongolia. We captured a total of 12 red foxes (8 females and 4 males and fi tted them with VHF radio-collars. Marked animals were tracked up to fi ve times a week to estimate home ranges. We also trapped small mammal and insects in different biotopes for 3 years to estimate relative abundance of prey. Our results showed that mean individual home range sizes varied widely and differed among years. There was variation in home ranges between adults versus juveniles, but no signifi cant difference was found between males versus females. In addition, mean home range size did not differ seasonally for pooled years. Variation in home ranges was best explained by a model that included covariates of year and age. We suggest that spatiotemporal changes in resource availability across years infl uenced home range dynamics of red foxes in our study.

Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.

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El-Hodiri, H; Bhatia-Dey, N; Kenyon, K; Ault, K; Dirksen, M; Jamrich, M

2001-01-01

Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.

FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

International Nuclear Information System (INIS)

Ma, Gui-Fen; Chen, Shi-Yao; Sun, Zhi-Rong; Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng; Ma, Li-Li; Lian, Jing-Jing; Song, Dong-Li

2013-01-01

Highlights: ► The article revealed FoxP3 gene function in gastric cancer firstly. ► Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. ► Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. ► Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. ► FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

Deletion of FoxO1 Leads to Shortening of QRS by Increasing Na+ Channel Activity through Enhanced Expression of both Cardiac NaV1.5 and β3 Subunit

OpenAIRE

Cai, Benzhi; Wang, Ning; Mao, Weike; You, Tao; Lu, Yan; Li, Xiang; Ye, Bo; Li, Faqian; Xu, Haodong

2014-01-01

Our in vitro studies revealed that a transcription factor, Forkhead box protein O1 (FoxO1), negatively regulates the expression of NaV1.5, a main α subunit of the cardiac Na+ channel, by altering the promoter activity of SCN5a in HL-1 cardiomyocytes. The in vivo role of FoxO1 in the regulation of cardiac NaV1.5 expression remains unknown. The present study aimed to define the role of FoxO1 in the regulation of NaV1.5 expression and cardiac Na+ channel activity in mouse ventricular cardiomyocy...

High glucose induced oxidative stress and apoptosis in cardiac microvascular endothelial cells are regulated by FoxO3a.

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Chaoming Peng

Full Text Available Cardiac microvascular endothelial cells (CMECs dysfunction contributes to cardiovascular complications in diabetes, whereas, the underlying mechanism is not fully clarified. FoxO transcription factors are involved in apoptosis and reactive oxygen species (ROS production. Therefore, the present study was designed to elucidate the potential role of FoxO3a on the CMECs injury induced by high glucose.CMECs were isolated from hearts of adult rats and cultured in normal or high glucose medium for 6 h, 12 h and 24 h respectively. To down-regulate FoxO3a expression, CMECs were transfected with FoxO3a siRNA. ROS accumulation and apoptosis in CMECs were assessed by dihydroethidine (DHE staining and TUNEL assay respectively. Moreover, the expressions of Akt, FoxO3a, Bim and BclxL in CMECs were assessed by Western blotting assay.ROS accumulation in CMECs was significantly increased after high glucose incubation for 6 to 24 h. Meanwhile, high glucose also increased apoptosis in CMECs, correlated with decreased the phosphorylation expressions of Akt and FoxO3a. Moreover, high glucose incubation increased the expression of Bim, whereas increased anti-apoptotic protein BclxL. Furthermore, siRNA target FoxO3a silencing enhanced the ROS accumulation, whereas suppressed apoptosis in CMECs. FoxO3a silencing also abolished the disturbance of Bcl-2 proteins induced by high glucose in CMECs.Our data provide evidence that high glucose induced FoxO3a activation which suppressed ROS accumulation, and in parallel, resulted in apoptosis of CMECs.

Nucleocytoplasmic shuttling of transcription factors

DEFF Research Database (Denmark)

Cartwright, P; Helin, K

2000-01-01

To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

Transcriptional regulation by competing transcription factor modules.

Directory of Open Access Journals (Sweden)

Rutger Hermsen

2006-12-01

Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

Associations between Forkhead Box O1 (FoxO1 Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid.

Directory of Open Access Journals (Sweden)

Asako Kinoshita

Full Text Available Forkhead box protein O1 (FoxO1 is a transcription factor which promotes hepatic glucose production (HGP by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively. Cows received 0 (LC-CON and HC-CON or 24 (LC-NA and HC-NA g/d nicotinic acid with high (HC or low (LC concentrate proportion from -42 days (-41.8 + 4.8; mean + standard deviation relative to expected calving date (d-42 to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1 and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1 were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA × concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation.

Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function

International Nuclear Information System (INIS)

Lieber, Charles S.; Leo, Maria Anna; Wang, Xiaolei; DeCarli, Leonore M.

2008-01-01

Chronic alcohol consumption affects the gene expression of a NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-γ coactivator1α (PGC-1α). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days. Alcohol increased hepatic mRNA expression of FoxO1 (p = 0.003) and p53 (p = 0.001) while corresponding protein levels remained unchanged. However phospho-FoxO1 and phospho-Akt (protein kinase) were both decreased by alcohol consumption (p = 0.04 and p = 0.02, respectively) while hepatic p53 was found hyperacetylated (p = 0.017). Furthermore, mitochondrial SIRT5 was reduced (p = 0.0025), and PGC-1α hyperacetylated (p = 0.027), establishing their role in protein modification. Thus, alcohol consumption disrupts nuclear-mitochondrial interactions by post-translation protein modifications, which contribute to alteration of mitochondrial biogenesis through the newly discovered reduction of SIRT5

FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Ma, Gui-Fen [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: shiyao_chen@163.com [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Sun, Zhi-Rong [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China); Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Li-Li; Lian, Jing-Jing [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Song, Dong-Li [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)

2013-01-11

Highlights: Black-Right-Pointing-Pointer The article revealed FoxP3 gene function in gastric cancer firstly. Black-Right-Pointing-Pointer Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. Black-Right-Pointing-Pointer Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. Black-Right-Pointing-Pointer Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Black-Right-Pointing-Pointer FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis

Fox-2 Splicing Factor Binds to a Conserved Intron Motif to PromoteInclusion of Protein 4.1R Alternative Exon 16

Energy Technology Data Exchange (ETDEWEB)

Ponthier, Julie L.; Schluepen, Christina; Chen, Weiguo; Lersch,Robert A.; Gee, Sherry L.; Hou, Victor C.; Lo, Annie J.; Short, Sarah A.; Chasis, Joel A.; Winkelmann, John C.; Conboy, John G.

2006-03-01

Activation of protein 4.1R exon 16 (E16) inclusion during erythropoiesis represents a physiologically important splicing switch that increases 4.1R affinity for spectrin and actin. Previous studies showed that negative regulation of E16 splicing is mediated by the binding of hnRNP A/B proteins to silencer elements in the exon and that downregulation of hnRNP A/B proteins in erythroblasts leads to activation of E16 inclusion. This paper demonstrates that positive regulation of E16 splicing can be mediated by Fox-2 or Fox-1, two closely related splicing factors that possess identical RNA recognition motifs. SELEX experiments with human Fox-1 revealed highly selective binding to the hexamer UGCAUG. Both Fox-1 and Fox-2 were able to bind the conserved UGCAUG elements in the proximal intron downstream of E16, and both could activate E16 splicing in HeLa cell co-transfection assays in a UGCAUG-dependent manner. Conversely, knockdown of Fox-2 expression, achieved with two different siRNA sequences resulted in decreased E16 splicing. Moreover, immunoblot experiments demonstrate mouse erythroblasts express Fox-2, but not Fox-1. These findings suggest that Fox-2 is a physiological activator of E16 splicing in differentiating erythroid cells in vivo. Recent experiments show that UGCAUG is present in the proximal intron sequence of many tissue-specific alternative exons, and we propose that the Fox family of splicing enhancers plays an important role in alternative splicing switches during differentiation in metazoan organisms.

Genetic signatures of adaptation revealed from transcriptome sequencing of Arctic and red foxes.

Science.gov (United States)

Kumar, Vikas; Kutschera, Verena E; Nilsson, Maria A; Janke, Axel

2015-08-07

The genus Vulpes (true foxes) comprises numerous species that inhabit a wide range of habitats and climatic conditions, including one species, the Arctic fox (Vulpes lagopus) which is adapted to the arctic region. A close relative to the Arctic fox, the red fox (Vulpes vulpes), occurs in subarctic to subtropical habitats. To study the genetic basis of their adaptations to different environments, transcriptome sequences from two Arctic foxes and one red fox individual were generated and analyzed for signatures of positive selection. In addition, the data allowed for a phylogenetic analysis and divergence time estimate between the two fox species. The de novo assembly of reads resulted in more than 160,000 contigs/transcripts per individual. Approximately 17,000 homologous genes were identified using human and the non-redundant databases. Positive selection analyses revealed several genes involved in various metabolic and molecular processes such as energy metabolism, cardiac gene regulation, apoptosis and blood coagulation to be under positive selection in foxes. Branch site tests identified four genes to be under positive selection in the Arctic fox transcriptome, two of which are fat metabolism genes. In the red fox transcriptome eight genes are under positive selection, including molecular process genes, notably genes involved in ATP metabolism. Analysis of the three transcriptomes and five Sanger re-sequenced genes in additional individuals identified a lower genetic variability within Arctic foxes compared to red foxes, which is consistent with distribution range differences and demographic responses to past climatic fluctuations. A phylogenomic analysis estimated that the Arctic and red fox lineages diverged about three million years ago. Transcriptome data are an economic way to generate genomic resources for evolutionary studies. Despite not representing an entire genome, this transcriptome analysis identified numerous genes that are relevant to arctic

Fox-2 protein regulates the alternative splicing of scleroderma-associated lysyl hydroxylase 2 messenger RNA.

Science.gov (United States)

Seth, Puneet; Yeowell, Heather N

2010-04-01

Scleroderma (systemic sclerosis [SSc]) is a complex connective tissue disorder characterized by hardening and thickening of the skin. One hallmark of scleroderma is excessive accumulation of collagen accompanied by increased levels of pyridinoline collagen crosslinks derived from hydroxylysine residues in the collagen telopeptide domains. Lysyl hydroxylase 2 (LH2), an important alternatively spliced enzyme in collagen biosynthesis, acts as a collagen telopeptide hydroxylase. Changes in the pattern of LH2 alternative splicing, favoring increased inclusion of the alternatively spliced LH2 exon 13A, thereby increasing the levels of the long transcript of LH2 (LH2[long]), are linked to scleroderma disease. This study was undertaken to examine the role played by RNA binding protein Fox-2 in regulating exon 13A inclusion, which leads to the generation of scleroderma-associated LH2(long) messenger RNA (mRNA). Phylogenetic sequence analysis of introns flanking exon 13A was performed. A tetracycline-inducible system in T-Rex 293 cells was used to induce Fox-2 protein, and endogenous LH2(long) mRNA was determined by reverse transcriptase-polymerase chain reaction. An LH2 minigene was designed, validated, and used in Fox-2 overexpression and mutagenesis experiments. Knockdown of Fox-2 was performed in mouse embryonic fibroblasts and in fibroblasts from SSc patients. Overexpression of Fox-2 enhanced the inclusion of exon 13A and increased the generation of LH2(long) mRNA, whereas knockdown of Fox-2 decreased LH2(long) transcripts. Mutational analysis of an LH2 minigene demonstrated that 2 of the 4 Fox binding motifs flanking LH2 exon 13A are required for inclusion of exon 13A. In early passage fibroblasts derived from patients with scleroderma, the knockdown of Fox-2 protein significantly decreased the endogenous levels of LH2(long) mRNA. Our findings indicate that Fox-2 plays an integral role in the regulation of LH2 splicing. Knockdown of Fox-2 and other methods to decrease

The Journey of a Transcription Factor

DEFF Research Database (Denmark)

Pireyre, Marie

Plants have developed astonishing networks regulating their metabolism to adapt to their environment. The complexity of these networks is illustrated by the expansion of families of regulators such as transcription factors in the plant kingdom. Transcription factors specifically impact...... transcriptional networks by integrating exogenous and endogenous stimuli and regulating gene expression accordingly. Regulation of transcription factors and their activation is thus highly important to modulate the transcriptional programs and increase fitness of the plant in a given environment. Plant metabolism....... The biosynthetic machinery of GLS is governed by interplay of six MYB and three bHLH transcription factors. MYB28, MYB29 and MYB76 regulate methionine-derived GLS, and MYB51, MYB34 and MYB122 regulate tryptophan-derived GLS. The three bHLH transcription factors MYC2, MYC3 and MYC4 physically interact with all six...

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

Science.gov (United States)

Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

A spring aerial census of red foxes in North Dakota

Science.gov (United States)

Sargeant, A.B.; Pfeifer, W.K.; Allen, S.H.

1975-01-01

Systematic aerial searches were flown on transects to locate adult red foxes (Vulpes vulpes), pups, and rearing dens on 559.4 km2 (six townships) in eastern North Dakota during mid-May and mid-June each year from 1969 through 1973 and during mid-April 1969 and early May 1970. The combined sightings of foxes and fox dens from the mid-May and mid-June searches were used to identify individual fox families. The number of fox families was used as the measurement of density. Dens, highly visible during the mid-May searches, were the most reliable family indicator; 84 percent of 270 families identified during the study were represented by dens. Adult foxes second in importance, were most observable during the mid-May searches when 20 to 35 percent of those estimated to be available were sighted. Adult sightings during other search periods ranged from 4 to 17 percent of those available. Pup sightings were the most variable family indicator, but they led to the discovery of some dens. Sources of error for which adjustment factors were determined are: den moves exceeding criterion established for the spacing of dens in a single family, overestimation of the number of fox families living near township boundaries, and the percentage of fox families overlooked during the aerial searches. These adjustment factors appeared to be largely compensatory.

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

Directory of Open Access Journals (Sweden)

Qian Chen

2016-12-01

region. Using a luciferase assay, we further observed that FoxO3a increased BNIP3L gene promoter activity. As expected, overexpression of BNIP3L in H9C2 cardiomyoblast cells reduced the cardioprotection of FGF-2 in H2O2-induced necrosis and mitochondrial dysfunction. Conclusions: The present data suggest that FGF-2 protects against H2O2-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway. Moreover, the present results demonstrate that FoxO3a is an important transcription factor that acts by binding to the promoter and promoting the transcription of BNIP3L, and it contributes to the necrosis and mitochondrial dysfunction induced by H2O2 in H9c2 cardiomyoblast cells.

Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA.

Science.gov (United States)

Lee, Ji-Won; Chen, Hui; Pullikotil, Philomena; Quon, Michael J

2011-02-25

FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). Therefore, we hypothesized that FoxO1 is a novel direct substrate for PKA-α. Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). Phosphorylation of wild-type FoxO1 (but not FoxO1-AAA) was detectable using phospho-specific antibodies. Similar results were obtained using purified GST-FoxO1 protein as the substrate. Thus, FoxO1 is a direct substrate for PKA-α in vitro. In bovine aortic endothelial cells, interaction between endogenous PKA-α and endogenous FoxO1 was detected by co-immunoprecipitation. In human aortic endothelial cells (HAEC), pretreatment with H89 (PKA inhibitor) or siRNA knockdown of PKA-α decreased forskolin- or prostaglandin E(2)-stimulated phosphorylation of FoxO1. In HAEC transfected with a FoxO-promoter luciferase reporter, co-expression of the catalytic domain of PKA-α, catalytically inactive mutant PKA-α, or siRNA against PKA-α caused corresponding increases or decreases in transactivation of the FoxO promoter. Expression of vascular cellular adhesion molecule-1 mRNA, up-regulated by FoxO1 in endothelial cells, was enhanced by siRNA knockdown of PKA-α or treatment of HAEC with the PKA inhibitor H89. Adhesion of monocytes to endothelial cells was enhanced by H89 treatment or overexpression of FoxO1-AAA, similar to effects of TNF-α treatment. We conclude that FoxO1 is a novel physiological substrate for PKA-α in vascular endothelial cells.

Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes)

Science.gov (United States)

2011-01-01

Background Two strains of the silver fox (Vulpes vulpes), with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed. Results cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence). Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p fox transcriptome. Conclusions Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information. PMID:21967120

Sequence comparison of prefrontal cortical brain transcriptome from a tame and an aggressive silver fox (Vulpes vulpes

Directory of Open Access Journals (Sweden)

Sun Qi

2011-10-01

Full Text Available Abstract Background Two strains of the silver fox (Vulpes vulpes, with markedly different behavioral phenotypes, have been developed by long-term selection for behavior. Foxes from the tame strain exhibit friendly behavior towards humans, paralleling the sociability of canine puppies, whereas foxes from the aggressive strain are defensive and exhibit aggression to humans. To understand the genetic differences underlying these behavioral phenotypes fox-specific genomic resources are needed. Results cDNA from mRNA from pre-frontal cortex of a tame and an aggressive fox was sequenced using the Roche 454 FLX Titanium platform (> 2.5 million reads & 0.9 Gbase of tame fox sequence; >3.3 million reads & 1.2 Gbase of aggressive fox sequence. Over 80% of the fox reads were assembled into contigs. Mapping fox reads against the fox transcriptome assembly and the dog genome identified over 30,000 high confidence fox-specific SNPs. Fox transcripts for approximately 14,000 genes were identified using SwissProt and the dog RefSeq databases. An at least 2-fold expression difference between the two samples (p Conclusions Transcriptome sequencing significantly expanded genomic resources available for the fox, a species without a sequenced genome. In a very cost efficient manner this yielded a large number of fox-specific SNP markers for genetic studies and provided significant insights into the gene expression profile of the fox pre-frontal cortex; expression differences between the two fox samples; and a catalogue of potentially important gene-specific sequence variants. This result demonstrates the utility of this approach for developing genomic resources in species with limited genomic information.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

Directory of Open Access Journals (Sweden)

Sabrina Murgan

Full Text Available In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain is directly required to restrict anterior neural development.

Directing traffic on DNA-How transcription factors relieve or induce transcriptional interference.

Science.gov (United States)

Hao, Nan; Palmer, Adam C; Dodd, Ian B; Shearwin, Keith E

2017-03-15

Transcriptional interference (TI) is increasingly recognized as a widespread mechanism of gene control, particularly given the pervasive nature of transcription, both sense and antisense, across all kingdoms of life. Here, we discuss how transcription factor binding kinetics strongly influence the ability of a transcription factor to relieve or induce TI.

TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

KAUST Repository

Schaefer, Ulf; Schmeier, Sebastian; Bajic, Vladimir B.

2010-01-01

The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

KAUST Repository

Schaefer, Ulf

2010-10-21

The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

The WRKY transcription factor family in Brachypodium distachyon.

Science.gov (United States)

Tripathi, Prateek; Rabara, Roel C; Langum, Tanner J; Boken, Ashley K; Rushton, Deena L; Boomsma, Darius D; Rinerson, Charles I; Rabara, Jennifer; Reese, R Neil; Chen, Xianfeng; Rohila, Jai S; Rushton, Paul J

2012-06-22

A complete assembled genome sequence of wheat is not yet available. Therefore, model plant systems for wheat are very valuable. Brachypodium distachyon (Brachypodium) is such a system. The WRKY family of transcription factors is one of the most important families of plant transcriptional regulators with members regulating important agronomic traits. Studies of WRKY transcription factors in Brachypodium and wheat therefore promise to lead to new strategies for wheat improvement. We have identified and manually curated the WRKY transcription factor family from Brachypodium using a pipeline designed to identify all potential WRKY genes. 86 WRKY transcription factors were found, a total higher than all other current databases. We therefore propose that our numbering system (BdWRKY1-BdWRKY86) becomes the standard nomenclature. In the JGI v1.0 assembly of Brachypodium with the MIPS/JGI v1.0 annotation, nine of the transcription factors have no gene model and eleven gene models are probably incorrectly predicted. In total, twenty WRKY transcription factors (23.3%) do not appear to have accurate gene models. To facilitate use of our data, we have produced The Database of Brachypodium distachyon WRKY Transcription Factors. Each WRKY transcription factor has a gene page that includes predicted protein domains from MEME analyses. These conserved protein domains reflect possible input and output domains in signaling. The database also contains a BLAST search function where a large dataset of WRKY transcription factors, published genes, and an extensive set of wheat ESTs can be searched. We also produced a phylogram containing the WRKY transcription factor families from Brachypodium, rice, Arabidopsis, soybean, and Physcomitrella patens, together with published WRKY transcription factors from wheat. This phylogenetic tree provides evidence for orthologues, co-orthologues, and paralogues of Brachypodium WRKY transcription factors. The description of the WRKY transcription factor

Fox Chase Network: Fox Chase Cancer Center's community hospital affiliation program.

Science.gov (United States)

Higman, S A; McKay, F J; Engstrom, P F; O'Grady, M A; Young, R C

2000-01-01

Fox Chase Cancer Center developed a format for affiliation with community providers in 1986. Fox Chase Network was formed to establish hospital-based community cancer centers to increase access to patients involved in clinical research. Under this program, the Fox Chase Network now contributes 500 patients per year to prevention and clinical research studies. As relationships with community providers form, patient referrals have increased at Fox Chase Cancer Center and for each Fox Chase Network member. A dedicated staff is required to operate the central office on a day-to-day basis as well as at each affiliate. We have found this to be a critical element in each program's success. New challenges in the cancer business-increasing volumes with declining revenue-have caused us to reconfigure the services offered to affiliates, while maintaining true to our mission: to reduce the burden of human cancer.

Echinococcus species from red foxes, corsac foxes, and wolves in Mongolia.

Science.gov (United States)

Ito, Akira; Chuluunbaatar, Gantigmaa; Yanagida, Tetsuya; Davaasuren, Anu; Sumiya, Battulga; Asakawa, Mitsuhiko; Ki, Toshiaki; Nakaya, Kazuhiro; Davaajav, Abmed; Dorjsuren, Temuulen; Nakao, Minoru; Sako, Yasuhito

2013-11-01

The small intestines of 420 wild canids (111 corsac foxes, 191 red foxes and 118 wolves) from Mongolia, were examined for adult worms of the genus Echinococcus. The Mongolian genotype of Echinococcus multilocularis was found in fifteen red foxes and four wolves, whereas two genotypes (G6/7 and G10) of Echinococcus canadensis were found in two and three wolves, respectively. No adult Echinococcus worms were found in the corsac foxes examined. The genotypes of E. multilocularis and E. canadensis are discussed in terms of host specificity and distribution in Mongolia. The importance of wolves in the completion of the life cycle of Echinococcus spp. is also discussed.

Different expression of FoxM1 in human benign and malignant pleural effusion.

Science.gov (United States)

Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

2015-01-01

The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

Fatty Acid–Regulated Transcription Factors in the Liver

Science.gov (United States)

Jump, Donald B.; Tripathy, Sasmita; Depner, Christopher M.

2014-01-01

Fatty acid regulation of hepatic gene transcription was first reported in the early 1990s. Several transcription factors have been identified as targets of fatty acid regulation. This regulation is achieved by direct fatty acid binding to the transcription factor or by indirect mechanisms where fatty acids regulate signaling pathways controlling the expression of transcription factors or the phosphorylation, ubiquitination, or proteolytic cleavage of the transcription factor. Although dietary fatty acids are well-established regulators of hepatic transcription factors, emerging evidence indicates that endogenously generated fatty acids are equally important in controlling transcription factors in the context of glucose and lipid homeostasis. Our first goal in this review is to provide an up-to-date examination of the molecular and metabolic bases of fatty acid regulation of key transcription factors controlling hepatic metabolism. Our second goal is to link these mechanisms to nonalcoholic fatty liver disease (NAFLD), a growing health concern in the obese population. PMID:23528177

A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.

Science.gov (United States)

Fox, Hannah L; Dembowski, Jill A; DeLuca, Neal A

2017-06-13

elongation factors to viral genomes and that in the absence of ICP22 viral transcription is globally reduced late in productive infection, due to an elongation defect. This insight defines a fundamental role of ICP22 in HSV-1 infection and elucidates the involvement of cellular factors in HSV-1 transcription. Copyright © 2017 Fox et al.

Dispersal patterns of red foxes relative to population density

Science.gov (United States)

Allen, Stephen H.; Sargeant, Alan B.

1993-01-01

Factors affecting red fox (Vulpes vulpes) dispersal patterns are poorly understood but warranted investigation because of the role of dispersal in rebuilding depleted populations and transmission of diseases. We examined dispersal patterns of red foxes in North Dakota based on recoveries of 363 of 854 foxes tagged as pups and relative to fox density. Foxes were recovered up to 8.6 years after tagging; 79% were trapped or shot. Straight-line distances between tagging and recovery locations ranged from 0 to 302 km. Mean recovery distances increased with age and were greater for males than females, but longest individual recovery distances were by females. Dispersal distances were not related to population density for males (P = 0.36) or females (P = 0.96). The proportion of males recovered that dispersed was inversely related to population density (r = -0.94; n = 5; P = 0.02), but not the proportion of females (r = -0.49; n = 5; P = 0.40). Dispersal directions were not uniform for either males (P = 0.003) or females (P = 0.006); littermates tended to disperse in similar directions (P = 0.09). A 4-lane interstate highway altered dispersal directions (P = 0.001). Dispersal is a strong innate behavior of red foxes (especially males) that results in many individuals of both sexes traveling far from natal areas. Because dispersal distance was unaffected by fox density, populations can be rebuilt and diseases transmitted long distances regardless of fox abundance.

The Transcription Factor Encyclopedia

DEFF Research Database (Denmark)

Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

2012-01-01

mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

The transcriptional repressor DREAM is involved in thyroid gene expression

International Nuclear Information System (INIS)

D'Andrea, Barbara; Di Palma, Tina; Mascia, Anna; Motti, Maria Letizia; Viglietto, Giuseppe; Nitsch, Lucio; Zannini, Mariastella

2005-01-01

Downstream regulatory element antagonistic modulator (DREAM) was originally identified in neuroendocrine cells as a calcium-binding protein that specifically binds to downstream regulatory elements (DRE) on DNA, and represses transcription of its target genes. To explore the possibility that DREAM may regulate the endocrine activity of the thyroid gland, we analyzed its mRNA expression in undifferentiated and differentiated thyroid cells. We demonstrated that DREAM is expressed in the normal thyroid tissue as well as in differentiated thyroid cells in culture while it is absent in FRT poorly differentiated cells. In the present work, we also show that DREAM specifically binds to DRE sites identified in the 5' untranslated region (UTR) of the thyroid-specific transcription factors Pax8 and TTF-2/FoxE1 in a calcium-dependent manner. By gel retardation assays we demonstrated that thapsigargin treatment increases the binding of DREAM to the DRE sequences present in Pax8 and TTF-2/Foxe1 5' UTRs, and this correlates with a significant reduction of the expression of these genes. Interestingly, in poorly differentiated thyroid cells overexpression of exogenous DREAM strongly inhibits Pax8 expression. Moreover, we provide evidence that a mutated form of DREAM unable to bind Ca 2+ interferes with thyroid cell proliferation. Therefore, we propose that in thyroid cells DREAM is a mediator of the calcium-signaling pathway and it is involved in the regulation of thyroid cell function

[Changes of FoxP3, CD4(+)CD25(+) regulatory T cells, TLR2 and TLR9 in children with infectious mononucleosis].

Science.gov (United States)

Wang, Qiang; Wang, Zuo-Feng; Cao, Mei; Wang, Zhi-Ying

2013-04-01

The aim of this study was to investigate the effects of TLR2, TLR9, CD4(+)CD25(+) regulatory T cells (Treg) and transcription factor FoxP3 in the pathogenesis of children with infectious mononucleosis (IM). Thirty-five acute IM patients admitted in our hospital from April 2010 to January 2011 were enrolled in this study. Thirty-five healthy subjects were taken as control. The thirty-five patients before treatment were considered as patients in acute stage, after treatment and without clinical symptom they were thought as patients in recovery stage. The expression levels of TLR2, TLR9 and FoxP3 mRNA were detected by real time PCR using SYBR Green I. The expression of T lymphocyte subset CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative levels of TLR2 mRNA (4.03 ± 0.56), TLR9 mRNA (8.88 ± 1.56) in peripheral blood mononuclear cells of IM patients in acute stage were significantly higher than those of the controls [TLR2 mRNA (2.22 ± 0.57), TLR9 mRNA (3.63 ± 1.30)] and IM patients in recovery stage [TLR2 mRNA (2.76 ± 0.83), TLR9 mRNA (5.34 ± 1.60)] (P 0.05). It is concluded that the expression of CD4(+)CD25(+)regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is down-regulated, but expression levels of TLR2 mRNA, TLR9 mRNA are up-regulated in IM patients of acute stage.

Red fox takeover of arctic fox breeding den : an observation from Yamal Peninsula, Russia

OpenAIRE

Rodnikova, Anna; Ims, Rolf Anker; Sokolov, Alexander; Skogstad, Gunhild; Sokolov, Vasily; Shtro, Victor; Fuglei, Eva

2011-01-01

Here, we report from the first direct observation of a red fox (Vulpes vulpes) intrusion on an arctic fox (Vulpes lagopus) breeding den from the southern Arctic tundra of Yamal Peninsula, Russia in 2007. At the same time, as a current range retraction of the original inhabitant of the circumpolar tundra zone the arctic fox is going on, the red fox is expanding their range from the south into arctic habitats. Thus, within large parts of the northern tundra areas the two species are sympatric w...

Arctic foxes, lemmings, and canada goose nest survival at cape Churchill, Manitoba

Science.gov (United States)

Reiter, M.E.; Andersen, D.E.

2011-01-01

We examined factors influencing Canada Goose (Branta canadensis interior) annual nest success, including the relative abundance of collared lemmings (Dicrostonyx richardsoni), arctic fox (Alopex lagopus) den occupancy, nest density, and spring phenology using data collected during annual Canada Goose breeding area surveys at Cape Churchill, Manitoba. Nest density and arctic fox den occupancy strongly influenced Canada Goose nest success. High nest density resulted in higher nest success and high den occupancy reduced nest success. Nest success was not influenced by lemming abundance in the current or previous year as predicted by the "bird-lemming" hypothesis. Reducing arctic fox abundance through targeted management increased nest survival of Canada Geese; a result that further emphasizes the importance of arctic fox as nest predators in this system. The spatial distribution of nest predators, at least for dispersed-nesting geese, may be most important for nest survival, regardless of the abundance of small mammals in the local ecosystem. Further understanding of the factors influencing the magnitude and variance in arctic fox abundance in this region, and the spatial scale at which these factors are realized, is necessary to fully explain predator-prey-alternative prey dynamics in this system. ?? 2011 by the Wilson Ornithological Society.

Characterization of the FoxL2 proximal promoter and coding sequence from the common snapping turtle (Chelydra serpentina).

Science.gov (United States)

Guo, Lei; Rhen, Turk

2017-10-01

Sex is determined by temperature during embryogenesis in snapping turtles, Chelydra serpentina. Previous studies in this species show that dihydrotestosterone (DHT) induces ovarian development at temperatures that normally produce males or mixed sex ratios. The feminizing effect of DHT is associated with increased expression of FoxL2, suggesting that androgens regulate transcription of FoxL2. To test this hypothesis, we cloned the proximal promoter (1.6kb) and coding sequence for snapping turtle FoxL2 (tFoxL2) in frame with mCherry to produce a fluorescent reporter. The tFoxL2-mCherry fusion plasmid or mCherry control plasmid were stably transfected into mouse KK1 granulosa cells. These cells were then treated with 0, 1, 10, or 100nM DHT to assess androgen effects on tFoxL2-mCherry expression. In contrast to the main hypothesis, DHT did not alter expression of the tFoxL2-mCherry reporter. However, normal serum increased expression of tFoxL2-mCherry when compared to charcoal-stripped serum, indicating that the cloned region of tFoxL2 contains cis regulatory elements. We also used the tFoxL2-mCherry plasmid as an expression vector to test the hypothesis that DHT and tFoxL2 interact to regulate expression of endogenous genes in granulosa cells. While tFoxL2-mCherry and DHT had independent effects on mouse FoxL2, FshR, GnRHR, and StAR expression, tFoxL2-mCherry potentiated low concentration DHT effects on mouse aromatase expression. Further studies will be required to determine whether synergistic regulation of aromatase by DHT and FoxL2 also occurs in turtle gonads during the sex-determining period, which would explain the feminizing effect of DHT in this species. Copyright © 2017 Elsevier Inc. All rights reserved.

Red fox predation on breeding ducks in midcontinent North America

Science.gov (United States)

Sargeant, Alan B.; Allen, Stephen H.; Eberhardt, Robert T.

1984-01-01

Red fox (Vulpes vulpes) predation on nesting ducks was assessed by examining 1,857 adult duck remains found at 1,432 fox rearing dens from 1968 to 1973. Dabbling ducks were much more vulnerable to foxes than diving ducks. Dabbling ducks (1,798) found at dens consisted of 27% blue-winged teals (Anas discors), 23% mallards (A. platyrhynchos), 20% northern pintails (A. acuta), 9% northern shovelers (Spatula clypeata), 8% gadwalls (A. strepera), 3% green-winged teals (A. crecca), 2% American wigeons (A. americana), and 10% unidentified. Relative abundance of individual species and nesting chronology were the most important factors affecting composition of ducks taken by foxes. Seventy-six percent of 1,376 adult dabbling ducks and 40% of 30 adult diving ducks for which sex was determined were hens. In western North Dakota and western South Dakota, 65% of mallard and northern pintail remains found at dens were hens compared with 76% in eastern North Dakota and eastern South Dakota (P fox predation rates on ducks. Predation rate indices ranged from 0.01 duck/den in Iowa to 1.80 ducks/den in eastern North Dakota. Average annual predation rate indices for dabbling ducks in a 3-county intensive study area in eastern North Dakota were closely correlated with May pond numbers (r = 0.874, P foxes than hens of late nesting species. Predation rate indices were expanded to estimate total numbers of ducks taken by fox families during the denning season. Estimated numbers of dabbling ducks taken annually by individual fox families in 2 physiographic regions comprising the intensive study area ranged from 16.1 to 65.9. Predation was highest during wet years and lowest during dry years and averaged lower, but was more variable, in the region where tillage was greatest and wetland water levels were least stable. Predation in the intensive study area averaged 2.97 adult dabbling ducks/ km2/year and represented an estimated average annual loss of 13.5% of hen and 4.5% of drake

GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis.

Science.gov (United States)

Wang, Lingdi; Scott, Iain; Zhu, Lu; Wu, Kaiyuan; Han, Kim; Chen, Yong; Gucek, Marjan; Sack, Michael N

2017-09-12

The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation. ERK inhibition restores FoxO1, gluconeogenic enzyme expression and glucose production. Reconstitution of mitochondrial-targeted GCN5L1 blunts mitochondrial ROS, ERK activation and increases FoxO1, gluconeogenic enzyme expression and hepatocyte glucose production. We suggest that mitochondrial GCN5L1 modulates post-translational control of FoxO1, regulates gluconeogenesis and controls metabolic pathways via mitochondrial ROS mediated ERK activation. Exploring mechanisms underpinning GCN5L1 mediated ROS signaling may expand our understanding of the role of mitochondria in gluconeogenesis control.Hepatic gluconeogenesis is tightly regulated at transcriptional level and is essential for survival during prolonged fasting. Here Wang et al. show that the mitochondrial enriched GCN5-like 1 protein controls hepatic glucose production by regulating FoxO1 protein levels via proteasome-dependent degradation and, in turn, gluconeogenic gene expression.

Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

Directory of Open Access Journals (Sweden)

Luciana Gabriel Nogueira

2014-01-01

Full Text Available Background. Chronic Chagas disease cardiomyopathy (CCC, a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC. Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13 or associated with Treg (TGF-β and IL-10 were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

Behavioral interactions of penned red and arctic foxes

Science.gov (United States)

Rudzinski, D.R.; Graves, H.B.; Sargeant, A.B.; Storm, G.L.

1982-01-01

Expansion of the geographical distribution of red foxes (Vulpes vulpes) into the far north tundra region may lead to competition between arctic (Alopex lagopus) and red foxes for space and resources. Behavioral interactions between red and arctic foxes were evaluated during 9 trials conducted in a 4.05-ha enclosure near Woodworth, North Dakota. Each trial consisted of introducing a male-female pair of arctic foxes into the enclosure and allowing them to acclimate for approximately a week before releasing a female red fox into the enclosure, followed by her mate a few days later. In 8 of 9 trials, red foxes were dominant over arctic foxes during encounters. Activity of the arctic foxes decreased upon addition of red foxes. Arctic foxes tried unsuccessfully to defend preferred den, resting, and feeding areas. Even though the outcome of competition between red and arctic foxes in the Arctic is uncertain, the more aggressive red fox can dominate arctic foxes in direct competition for den sites and other limited resources.

FoxP3+CD4+CD25+ T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease

Science.gov (United States)

Kelsen, J; Agnholt, J; Hoffmann, H J; Rømer, J L; Hvas, C L; Dahlerup, J F

2005-01-01

CD4+CD25+ regulatory T cells (Tregs) are involved in the maintenance of peripheral tolerance and ensure a balanced immune response competent of fighting pathogens and at the same time recognizing commensals as harmless. This feature is lost in Crohn's disease (CD). The forkhead/winged helix transcription factor FoxP3 is a master gene for Treg function and defects in the FoxP3 gene lead to a clinical picture similar to inflammatory bowel disease (IBD). Murine colitis can be cured by adoptive transfer of Tregs and ex vivo-generated gut-specific Tregs represent an attractive option for therapy in CD. Thus, defective Tregs could contribute to the development of CD. We cultured biopsies of colonic mucosa in the presence of high concentrations of interleukin (IL)-2 and IL-4 to overcome the anergic nature of naturally occurring CD4+CD25+ Tregs in the mucosa. We investigated the expression of FoxP3 and regulatory potential of gut-derived CD4+CD25+ T cells cultured from patients with CD and healthy individuals. The FoxP3 expression was analysed by reverse transcriptase polymerase chain reaction (RT-PCR), and the suppressive effect of FoxP3+CD4+CD25+ T cells on proliferation and cytokine production of autologous CD4+ T cells was assessed by flow cytometry. Cultured gut-derived T cells with CD4+CD25+ phenotype expressed FoxP3 and were able as the freshly isolated Tregs from peripheral blood to suppress proliferation and cytokine production of autologous CD4+ T cells. Thus, we demonstrate that FoxP3+CD4+CD25+ T cells with regulatory properties can be propagated in vitro from inflamed mucosa of CD patients, which may be of interest in adoptive immunotherapy. PMID:16045746

AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

Science.gov (United States)

Zhao, Shanchao; Bao, Jiming; Song, Xianlu

2016-01-01

Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (Cls) were calculated by comparing the minor and major alleles. Results A total of seven articles reporting associations of FOX03A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rsI3217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR =1.36, 95% CI, 1. 10–1.69, P=0.005; OR =1.20, 95% CI, 1.04–1.37, P=0.01; OR =1.27, 95% CI, 1.10–1.46, P=0.001; OR =1.14, 95% CI, 1.01–1.27 and OR =1.24, 95% CI, 1.07–1.43, P=0.003, respectively). Analysis is stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =1.54, 95% CI, 1.33–1.79, P<0.001; OR =1.38, 95% CI, 1.15–1.66, P=0.001; and OR =1.39, 95% CI, 1.15–1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. Conclusions In conclusion, this meta-analysis indicates a significant association of five FOX03A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

Diet patterns of island foxes on San Nicolas Island relative to feral cat removal

Science.gov (United States)

Cypher, Brian L.; Kelly, Erica C.; Ferrara, Francesca J.; Drost, Charles A.; Westall, Tory L.; Hudgens, Brian

2017-01-01

Island foxes (Urocyon littoralis) are a species of conservation concern that occur on six of the Channel Islands off the coast of southern California. We analysed island fox diet on San Nicolas Island during 2006–12 to assess the influence of the removal of feral cats (Felis catus) on the food use by foxes. Our objective was to determine whether fox diet patterns shifted in response to the cat removal conducted during 2009–10, thus indicating that cats were competing with foxes for food items. We also examined the influence of annual precipitation patterns and fox abundance on fox diet. On the basis of an analysis of 1975 fox scats, use of vertebrate prey – deer mice (Peromyscus maniculatus), birds, and lizards – increased significantly during and after the complete removal of cats (n = 66) from the island. Deer mouse abundance increased markedly during and after cat removal and use of mice by foxes was significantly related to mouse abundance. The increase in mice and shift in item use by the foxes was consistent with a reduction in exploitative competition associated with the cat removal. However, fox abundance declined markedly coincident with the removal of cats and deer mouse abundance was negatively related to fox numbers. Also, annual precipitation increased markedly during and after cat removal and deer mouse abundance closely tracked precipitation. Thus, our results indicate that other confounding factors, particularly precipitation, may have had a greater influence on fox diet patterns.

The plateau zokors' learning and memory ability is related to the high expression levels of foxP2 in the brain.

Science.gov (United States)

Ma, Ben-Yuan; Wei, Lian; Sun, Sheng-Zhen; Wang, Duo-Wei; Wei, Deng-Bang

2014-04-25

Plateau zokor (Myospalax baileyi) is a subterranean mammal. Plateau zokor has high learning and memory ability, and can determine the location of blocking obstacles in their tunnels. Forkhead box p2 (FOXP2) is a transcription factor implicated in the neural control of orofacial coordination and sensory-motor integration, particularly with respect to learning, memory and vocalization. To explore the association of foxP2 with the high learning and memory ability of plateau zokor, the cDNA of foxP2 of plateau zokor was sequenced; by using plateau pika as control, the expression levels of foxP2 mRNA and FOXP2 protein in brain of plateau zokor were determined by real-time PCR and Western blot, respectively; and the location of FOXP2 protein in the brain of plateau zokor was determined by immunohistochemistry. The result showed that the cDNA sequence of plateau zokor foxP2 was similar to that of other mammals and the amino acid sequences showed a relatively high degree of conservation, with the exception of two particular amino acid substitutions [a Gln (Q)-to-His (H) change at position 231 and a Ser (S)-to-Ile (I) change at position 235]. Higher expression levels of foxP2 mRNA (3-fold higher) and FOXP2 protein (>2-fold higher) were detected in plateau zokor brain relative to plateau pika brain. In plateau zokor brain, FOXP2 protein was highly expressed in the cerebral cortex, thalamus and the striatum (a basal ganglia brain region). The results suggest that the high learning and memory ability of plateau zokor is related to the high expression levels of foxP2 in the brain.

NAC transcription factors: structurally distinct, functionally diverse

DEFF Research Database (Denmark)

Olsen, Addie Nina; Ernst, Heidi A; Leggio, Leila Lo

2005-01-01

level and localization, and to the first indications of NAC participation in transcription factor networks. The recent determination of the DNA and protein binding NAC domain structure offers insight into the molecular functions of the protein family. Research into NAC transcription factors has......NAC proteins constitute one of the largest families of plant-specific transcription factors, and the family is present in a wide range of land plants. Here, we summarize the biological and molecular functions of the NAC family, paying particular attention to the intricate regulation of NAC protein...

FOOD OF THE SILVER FOX VULPES CHAMA The silver fox Vulpes ...

African Journals Online (AJOL)

habits as follows: "The South African Silver Fox is nocturnal, occasionally crepuscular, and goes about singly or in ... stigma attached to virtually any "fox" or "jackal" in southern Africa as killers offarm animals. Thus many ... of data for the species justifies pUblication of the results, while further work continues. MATERIAL AND ...

A transcription factor active on the epidermal growth factor receptor gene

International Nuclear Information System (INIS)

Kageyama, R.; Merlino, G.T.; Pastan, I.

1988-01-01

The authors have developed an in vitro transcription system for the epidermal growth factor receptor (EGFR) oncogene by using nuclear extracts of A431 human epidermoid carcinoma cells, which overproduce EGFR. They found that a nuclear factor, termed EGFR-specific transcription factor (ETF), specifically stimulated EGFR transcription by 5- to 10-fold. In this report, ETF, purified by using sequence-specific oligonucleotide affinity chromatography, is shown by renaturing material eluted from a NaDodSO 4 /polyacrylamide gel to be a protein with a molecular mass of 120 kDa. ETF binds to the promoter region, as measured by DNase I footprinting and gel-mobility-shift assays, and specifically stimulates the transcription of the EGFR gene in a reconstituted in vitro transcription system. These results suggest that ETF could play a role in the overexpression of the cellular oncogene EGFR

FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch

Science.gov (United States)

Day, Nancy F; Kimball, Todd Haswell; Aamodt, Caitlin M; Heston, Jonathan B; Hilliard, Austin T; Xiao, Xinshu; White, Stephanie A

2018-01-01

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans. PMID:29360038

Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

Directory of Open Access Journals (Sweden)

Chan-on W

2015-04-01

Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

Missense polymorphisms in the MC1R gene of the dog, red fox, arctic fox and Chinese raccoon dog.

Science.gov (United States)

Nowacka-Woszuk, J; Salamon, S; Gorna, A; Switonski, M

2013-04-01

Coat colour variation is determined by many genes, one of which is the melanocortin receptor type 1 (MC1R) gene. In this study, we examined the whole coding sequence of this gene in four species belonging to the Canidae family (dog, red fox, arctic fox and Chinese raccoon dog). Although the comparative analysis of the obtained nucleotide sequences revealed a high conservation, which varied between 97.9 and 99.1%, we altogether identified 22 SNPs (10 in dogs, six in farmed red foxes, two in wild red foxes, three in arctic foxes and one in Chinese raccoon dog). Among them, seven appeared to be novel: one silent in the dog, three missense and one silent in the red fox, one in the 3'-flanking region in the arctic fox and one silent in the Chinese raccoon dog. In dogs and red foxes, the SNPs segregated as 10 and four haplotypes, respectively. Taking into consideration the published reports and results of this study, the highest number of missense polymorphisms was until now found in the dog (9) and red fox (7). © 2012 Blackwell Verlag GmbH.

DNA residence time is a regulatory factor of transcription repression

Science.gov (United States)

Clauß, Karen; Popp, Achim P.; Schulze, Lena; Hettich, Johannes; Reisser, Matthias; Escoter Torres, Laura; Uhlenhaut, N. Henriette

2017-01-01

Abstract Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains. We characterized the DNA residence times of our repressors in living cells using single molecule tracking. The residence times depended non-linearly on the number of repeat domains and differed by more than a factor of six. The factors provoked a residence time-dependent decrease in transcript level of the glucocorticoid receptor-activated gene SGK1. Down regulation of transcription was due to a lower burst frequency in the presence of long binding repressors and is in accordance with a model of competitive inhibition of endogenous activator binding. Our single molecule experiments reveal transcription factor DNA residence time as a regulatory factor controlling transcription repression and establish TALE-DNA binding domains as tools for the temporal dissection of transcription regulation. PMID:28977492

Tanshinol Attenuates the Deleterious Effects of Oxidative Stress on Osteoblastic Differentiation via Wnt/FoxO3a Signaling

Directory of Open Access Journals (Sweden)

Yajun Yang

2013-01-01

Full Text Available There is now increasing evidence which suggests a pivotal role for oxidative stress in the development and progression of osteoporosis. We confirm herein the protective effects of natural antioxidant Tanshinol against oxidative stress in osteoblastic differentiation and the underlying mechanism. Our results show that hydrogen peroxide (H2O2 leads to accumulation of reactive oxygen species (ROS, decrease in cell viability, cell cycle arrest and apoptosis in a caspase-3-dependent manner, and inhibition of osteoblastic differentiation. Tanshinol reverses these deleterious consequence triggered by oxidative stress. Moreover, under the condition of oxidative stress, Tanshinol suppresses the activation of FoxO3a transcription factor and expressions of its target genes Gadd45a and catalase (CAT and simultaneously counteracts the inhibition of Wnt signalling and expressions of target genes Axin2, alkaline phosphatase (ALP, and Osteoprotegerin (OPG. The findings are further consolidated using FoxO3a siRNA interference and overexpression of Tcf4. The results illustrate that Tanshinol attenuates oxidative stress via down-regulation of FoxO3a signaling, and rescues the decrease of osteoblastic differentiation through upregulation of Wnt signal under oxidative stress. The present findings suggest that the beneficial effects of Tanshinol may be adopted as a novel therapeutic approach in recently recognized conditions of niche targeting osteoporosis.

Runx transcription factors in neuronal development

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Shiga Takashi

2008-08-01

Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

Application of a Real-time Reverse Transcription Loop Mediated Amplification Method to the Detection of Rabies Virus in Arctic Foxes in Greenland

DEFF Research Database (Denmark)

Wakeley, Philip; Johnson, Nicholas; Rasmussen, Thomas Bruun

Reverse transcription loop mediated amplification (RT-LAMP) offers a rapid, isothermal method for amplification of virus RNA. In this study a panel of positive rabies virus samples originally prepared from arctic fox brain tissue was assessed for the presence of rabies viral RNA using a real time...... RT-LAMP. The method had previously been shown to work with samples from Ghana which clustered with cosmopolitan lineage rabies viruses but the assay had not been assessed using samples from animals infected with rabies from the arctic region. The assay is designed to amplify both cosmopolitan strains...... and arctic-like strains of classical rabies virus due to the primer design and is therefore expected to be universally applicable independent of region of the world where the virus is isolated. Of the samples tested all were found to be positive after incubation for 25 to 30 minutes. The method made use...

FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

DEFF Research Database (Denmark)

Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

2011-01-01

Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA.

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Dustin L Updike

2006-09-01

Full Text Available The histone variant H2A.Z is evolutionarily conserved and plays an essential role in mice, Drosophila, and Tetrahymena. The essential function of H2A.Z is unknown, with some studies suggesting a role in transcriptional repression and others in activation. Here we show that Caenorhabditis elegans HTZ-1/H2A.Z and the remodeling complex MYS-1/ESA1-SSL-1/SWR1 synergize with the FoxA transcription factor PHA-4 to coordinate temporal gene expression during foregut development. We observe dramatic genetic interactions between pha-4 and htz-1, mys-1, and ssl-1. A survey of transcription factors reveals that this interaction is specific, and thus pha-4 is acutely sensitive to reductions in these three proteins. Using a nuclear spot assay to visualize HTZ-1 in living embryos as organogenesis proceeds, we show that HTZ-1 is recruited to foregut promoters at the time of transcriptional onset, and this recruitment requires PHA-4. Loss of htz-1 by RNAi is lethal and leads to delayed expression of a subset of foregut genes. Thus, the effects of PHA-4 on temporal regulation can be explained in part by recruitment of HTZ-1 to target promoters. We suggest PHA-4 and HTZ-1 coordinate temporal gene expression by modulating the chromatin environment.

Y-Chromosome Markers for the Red Fox.

Science.gov (United States)

Rando, Halie M; Stutchman, Jeremy T; Bastounes, Estelle R; Johnson, Jennifer L; Driscoll, Carlos A; Barr, Christina S; Trut, Lyudmila N; Sacks, Benjamin N; Kukekova, Anna V

2017-09-01

The de novo assembly of the red fox (Vulpes vulpes) genome has facilitated the development of genomic tools for the species. Efforts to identify the population history of red foxes in North America have previously been limited by a lack of information about the red fox Y-chromosome sequence. However, a megabase of red fox Y-chromosome sequence was recently identified over 2 scaffolds in the reference genome. Here, these scaffolds were scanned for repeated motifs, revealing 194 likely microsatellites. Twenty-three of these loci were selected for primer development and, after testing, produced a panel of 11 novel markers that were analyzed alongside 2 markers previously developed for the red fox from dog Y-chromosome sequence. The markers were genotyped in 76 male red foxes from 4 populations: 7 foxes from Newfoundland (eastern Canada), 12 from Maryland (eastern United States), and 9 from the island of Great Britain, as well as 48 foxes of known North American origin maintained on an experimental farm in Novosibirsk, Russia. The full marker panel revealed 22 haplotypes among these red foxes, whereas the 2 previously known markers alone would have identified only 10 haplotypes. The haplotypes from the 4 populations clustered primarily by continent, but unidirectional gene flow from Great Britain and farm populations may influence haplotype diversity in the Maryland population. The development of new markers has increased the resolution at which red fox Y-chromosome diversity can be analyzed and provides insight into the contribution of males to red fox population diversity and patterns of phylogeography. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

Shukla, Shatrunajay [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Sharma, Ankita [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Pandey, Vivek Kumar [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India); Raisuddin, Sheikh [Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi ‐110062 (India); Kakkar, Poonam, E-mail: kakkarp59@gmail.com [Herbal Research Section, CSIR — Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow‐226001 (India); Academy of Scientific and Innovative Research (India)

2016-01-15

Post-translational modifications i.e. phosphorylation and acetylation are pivotal requirements for proper functioning of eukaryotic proteins. The current study aimed to decode the impact of acetylation/deacetylation of non-histone targets i.e. FoxO1/3a and p53 of sirtuins (NAD{sup +} dependent enzymes with lysine deacetylase activity) in berberine treated human hepatoma cells. Berberine (100 μM) inhibited sirtuins significantly (P < 0.05) at transcriptional level as well as at translational level. Combination of nicotinamide (sirtuin inhibitor) with berberine potentiated sirtuins inhibition and increased the expression of FoxO1/3a and phosphorylation of p53 tumor suppressor protein. As sirtuins deacetylate non-histone targets including FoxO1/3a and p53, berberine increased the acetylation load of FoxO1/3a and p53 proteins. Acetylated FoxO and p53 proteins transcriptionally activate BH3-only proteins Bim and PUMA (3.89 and 3.87 fold respectively, P<0.001), which are known as direct activator of pro-apoptotic Bcl-2 family protein Bax that culminated into mitochondria mediated activation of apoptotic cascade. Bim/PUMA knock-down showed no changes in sirtuins' expression while cytotoxicity induced by berberine and nicotinamide was curtailed up to 28.3% (P < 0.001) and it restored pro/anti apoptotic protein ratio in HepG2 cells. Sirtuins inhibition was accompanied by decline in NAD{sup +}/NADH ratio, ATP generation, enhanced ROS production and decreased mitochondrial membrane potential. TEM analysis confirmed mitochondrial deterioration and cell damage. SRT-1720 (1–10 μM), a SIRT-1 activator, when pre-treated with berberine (25 μM), reversed sirtuins expression comparable to control and significantly restored the cell viability (P < 0.05). Thus, our findings suggest that berberine mediated sirtuins inhibition resulting into FoxO1/3a and p53 acetylation followed by BH3-only protein Bim/PUMA activation may in part be responsible for mitochondria

Potential Role of Activating Transcription Factor 5 during Osteogenesis

Directory of Open Access Journals (Sweden)

Luisa Vicari

2016-01-01

Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

Potential Role of Activating Transcription Factor 5 during Osteogenesis.

Science.gov (United States)

Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

2016-01-01

Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

Polyphenol Compound as a Transcription Factor Inhibitor.

Science.gov (United States)

Park, Seyeon

2015-10-30

A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).

Angiostrongylus vasorum in Romania: an extensive survey in red foxes, Vulpes vulpes.

Science.gov (United States)

Deak, Georgiana; Gherman, Călin M; Ionică, Angela M; Vezendan, Alexandru D; D'Amico, Gianluca; Matei, Ioana A; Daskalaki, Aikaterini A; Marian, Ionuț; Damian, Aurel; Cozma, Vasile; Mihalca, Andrei D

2017-07-12

Angiostrongylus vasorum is the causative agent of canine angiostrongylosis, a severe snail-borne disease of dogs. Red foxes are important natural reservoirs of infection, and surveys of foxes provide a more objective picture of the parasite distribution. Our aim was to investigate the possibility of the presence of A. vasorum in red foxes from the western part of Romania and to analyse the risk factors related to the sex, age and geographic origin of the foxes. Between July 2016 and April 2017, 567 hunted red foxes from 10 counties of western Romania were examined by necropsy for the presence of lungworms. Overall, the infection with A. vasorum has been found in 24 red foxes (4.2%) originating in four counties (Mureș, Hunedoara, Sălaj and Cluj). There was no significant difference between the prevalence in males and females, between juveniles and adults and between counties. This is the first report of autochthonous infections of A. vasorum in Romania, showing a relatively low prevalence and extending eastwards the known distributional range of this parasite in Europe. The presence of autochthonous cases in domestic dogs in Romania remains to be confirmed by further studies.

Sarcoptic Mange in a South American Gray Fox (Chilla Fox; Lycalopex griseus ), Chile.

Science.gov (United States)

Verdugo, Claudio; Espinoza, Angelo; Moroni, Manuel; Valderrama, Rocio; Hernandez, Carlos

2016-07-01

Mange, a prevalent disease of dogs in Chile, is also a serious threat to wildlife. We report a case of sarcoptic mange in a South American gray fox or chilla fox ( Lycalopex griseus ). Further research is needed to understand the impact of mange in wildlife populations.

SoyDB: a knowledge database of soybean transcription factors

Directory of Open Access Journals (Sweden)

Valliyodan Babu

2010-01-01

Full Text Available Abstract Background Transcription factors play the crucial rule of regulating gene expression and influence almost all biological processes. Systematically identifying and annotating transcription factors can greatly aid further understanding their functions and mechanisms. In this article, we present SoyDB, a user friendly database containing comprehensive knowledge of soybean transcription factors. Description The soybean genome was recently sequenced by the Department of Energy-Joint Genome Institute (DOE-JGI and is publicly available. Mining of this sequence identified 5,671 soybean genes as putative transcription factors. These genes were comprehensively annotated as an aid to the soybean research community. We developed SoyDB - a knowledge database for all the transcription factors in the soybean genome. The database contains protein sequences, predicted tertiary structures, putative DNA binding sites, domains, homologous templates in the Protein Data Bank (PDB, protein family classifications, multiple sequence alignments, consensus protein sequence motifs, web logo of each family, and web links to the soybean transcription factor database PlantTFDB, known EST sequences, and other general protein databases including Swiss-Prot, Gene Ontology, KEGG, EMBL, TAIR, InterPro, SMART, PROSITE, NCBI, and Pfam. The database can be accessed via an interactive and convenient web server, which supports full-text search, PSI-BLAST sequence search, database browsing by protein family, and automatic classification of a new protein sequence into one of 64 annotated transcription factor families by hidden Markov models. Conclusions A comprehensive soybean transcription factor database was constructed and made publicly accessible at http://casp.rnet.missouri.edu/soydb/.

Radiation activation of transcription factors in mammalian cells

International Nuclear Information System (INIS)

Kraemer, M.; Stein, B.; Mai, S.; Kunz, E.; Koenig, H.; Ponta, H.; Herrlich, P.; Rahmsdorf, H.J.; Loferer, H.; Grunicke, H.H.

1990-01-01

In mammalian cells radiation induces the enhanced transcription of several genes. The cis acting elements in the control region of inducible genes have been delimited by site directed mutagenesis. Several different elements have been found in different genes. They do not only activate gene transcription in response to radiation but also in response to growth factors and to tumor promoter phorbol esters. The transcription factors binding to these elements are present also in non-irradiated cells, but their DNA binding activity and their transactivating capability is increased upon irradiation. The signal chain linking the primary radiation induced signal (damaged DNA) to the activation of transcription factors involves the action of (a) protein kinase(s). (orig.)

Are flying-foxes coming to town? Urbanisation of the spectacled flying-fox (Pteropus conspicillatus in Australia.

Directory of Open Access Journals (Sweden)

Jessica Tait

Full Text Available Urbanisation of wildlife populations is a process with significant conservation and management implications. While urban areas can provide habitat for wildlife, some urbanised species eventually come into conflict with humans. Understanding the process and drivers of wildlife urbanisation is fundamental to developing effective management responses to this phenomenon. In Australia, flying-foxes (Pteropodidae are a common feature of urban environments, sometimes roosting in groups of tens of thousands of individuals. Flying-foxes appear to be becoming increasingly urbanised and are coming into increased contact and conflict with humans. Flying-fox management is now a highly contentious issue. In this study we used monitoring data collected over a 15 year period (1998-2012 to examine the spatial and temporal patterns of association of spectacled flying-fox (Pteropus conspicillatus roost sites (camps with urban areas. We asked whether spectacled flying-foxes are becoming more urbanised and test the hypothesis that such changes are associated with anthropogenic changes to landscape structure. Our results indicate that spectacled flying-foxes were more likely to roost near humans than might be expected by chance, that over the period of the study the proportion of the flying-foxes in urban-associated camps increased, as did the number of urban camps. Increased urbanisation of spectacled flying-foxes was not related to changes in landscape structure or to the encroachment of urban areas on camps. Overall, camps tended to be found in areas that were more fragmented, closer to human habitation and with more urban land cover than the surrounding landscape. This suggests that urbanisation is a behavioural response rather than driven by habitat loss.

Comparison of Transcription Factor Binding Site Models

KAUST Repository

Bhuyan, Sharifulislam

2012-05-01

Modeling of transcription factor binding sites (TFBSs) and TFBS prediction on genomic sequences are important steps to elucidate transcription regulatory mechanism. Dependency of transcription regulation on a great number of factors such as chemical specificity, molecular structure, genomic and epigenetic characteristics, long distance interaction, makes this a challenging problem. Different experimental procedures generate evidence that DNA-binding domains of transcription factors show considerable DNA sequence specificity. Probabilistic modeling of TFBSs has been moderately successful in identifying patterns from a family of sequences. In this study, we compare performances of different probabilistic models and try to estimate their efficacy over experimental TFBSs data. We build a pipeline to calculate sensitivity and specificity from aligned TFBS sequences for several probabilistic models, such as Markov chains, hidden Markov models, Bayesian networks. Our work, containing relevant statistics and evaluation for the models, can help researchers to choose the most appropriate model for the problem at hand.

An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10

Directory of Open Access Journals (Sweden)

Pavan William J

2008-10-01

Full Text Available Abstract Background A major challenge lies in understanding the complexities of gene regulation. Mutation of the transcription factor SOX10 is associated with several human diseases. The disease phenotypes reflect the function of SOX10 in diverse tissues including the neural crest, central nervous system and otic vesicle. As expected, the SOX10 expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern. SOX10 expression is highly conserved between all vertebrates characterised. Results We have combined in vivo testing of DNA fragments in zebrafish and computational comparative genomics to identify the first regulatory regions of the zebrafish sox10 gene. Both approaches converged on the 3' end of the conserved 1st intron as being critical for spatial patterning of sox10 in the embryo. Importantly, we have defined a minimal region crucial for this function. We show that this region contains numerous binding sites for transcription factors known to be essential in early neural crest induction, including Tcf/Lef, Sox and FoxD3. We show that the identity and relative position of these binding sites are conserved between zebrafish and mammals. A further region, partially required for oligodendrocyte expression, lies in the 5' region of the same intron and contains a putative CSL binding site, consistent with a role for Notch signalling in sox10 regulation. Furthermore, we show that β-catenin, Notch signalling and Sox9 can induce ectopic sox10 expression in early embryos, consistent with regulatory roles predicted from our transgenic and computational results. Conclusion We have thus identified two major sites of sox10 regulation in vertebrates and provided evidence supporting a role for at least three factors in driving sox10 expression in neural crest, otic epithelium and oligodendrocyte domains.

Crystallization and preliminary crystallographic studies of FoxE from Rhodobacter ferrooxidans SW2, an FeII oxidoreductase involved in photoferrotrophy

International Nuclear Information System (INIS)

Pereira, L.; Saraiva, I. H.; Coelho, R.; Newman, D. K.; Louro, R. O.; Frazão, C.

2012-01-01

Crystals of the R. ferrooxidans SW2 iron oxidoreductase FoxE were obtained and the phase problem was solved by Fe SAD at 2.44 Å resolution. FoxE is a protein encoded by the foxEYZ operon of Rhodobacter ferrooxidans SW2 that is involved in Fe II -based anoxygenic photosynthesis (‘photoferrotrophy’). It is thought to reside in the periplasm, where it stimulates light-dependent Fe II oxidation. It contains 259 residues, including two haem c-binding motifs. As no three-dimensional model is available and there is no structure with a similar sequence, crystals of FoxE were produced. They diffracted to 2.44 Å resolution using synchrotron radiation at the Fe edge. The phase problem was solved by SAD using SHELXC/D/E and the experimental maps confirmed the presence of two haems per molecule

Forkhead box protein A2, a pioneer factor for hepatogenesis, is involved in the expression of hepatic phenotype of alpha-fetoprotein-producing adenocarcinoma.

Science.gov (United States)

Yamamura, Nobuhisa; Fugo, Kazunori; Kishimoto, Takashi

2017-09-01

Alpha-fetoprotein (AFP)-producing adenocarcinoma is a high-malignant variant of adenocarcinoma with a hepatic or fetal-intestinal phenotype. The number of cases of AFP-producing adenocarcinomas is increasing, but the molecular mechanism underlying the aberrant production of AFP is unclear. Here we sought to assess the role of Forkhead box A (FoxA)2, which is a pioneer transcription factor in the differentiation of hepatoblasts. FoxA2 expression was investigated in five cases of AFP-producing gastric adenocarcinomas by immunohistochemistry, and all cases showed FoxA2 expression. Chromatin immunoprecipitation revealed the DNA binding of FoxA2 on the regulatory element of AFP gene in AFP-producing adenocarcinoma cells. The inhibition of FoxA2 expression with siRNA reduced the mRNA expression of liver-specific proteins, including AFP, albumin, and transferrin. The inhibition of FoxA2 also reduced the expressions of liver-enriched nuclear factors, i.e., hepatocyte nuclear factor (HNF) 4α and HNF6, although the expressions of HNF1α and HNF1β were not affected. The same effect as FoxA2 knockdown in AFP producing adenocarcinoma cells was also observed in hepatocellular carcinoma cells. Our results suggest that FoxA2 plays a key role in the expression of hepatic phenotype of AFP-producing adenocarcinomas. Copyright © 2017 Elsevier GmbH. All rights reserved.

Michael J. Fox Foundation for Parkinson's Research

Science.gov (United States)

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Polyphenol Compound as a Transcription Factor Inhibitor

Directory of Open Access Journals (Sweden)

Seyeon Park

2015-10-01

Full Text Available A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor–DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein–protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1, c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and β-catenin/T cell factor (Tcf.

Effect of British hunting ban on fox numbers.

Science.gov (United States)

Baker, Philip J; Harris, Stephen; Webbon, Charlotte C

2002-09-05

Pressure to ban the hunting of foxes with hounds in Britain has fuelled debate about its contribution to the control of fox populations. We took advantage of a nationwide one-year ban on fox-hunting during the outbreak of foot-and-mouth disease (FMD) in 2001 to examine this issue and found that the ban had no measurable impact on fox numbers in randomly selected areas. Our results argue against suggestions that fox populations would increase markedly in the event of a permanent ban on hunting.

Protein-protein interactions in the regulation of WRKY transcription factors.

Science.gov (United States)

Chi, Yingjun; Yang, Yan; Zhou, Yuan; Zhou, Jie; Fan, Baofang; Yu, Jing-Quan; Chen, Zhixiang

2013-03-01

It has been almost 20 years since the first report of a WRKY transcription factor, SPF1, from sweet potato. Great progress has been made since then in establishing the diverse biological roles of WRKY transcription factors in plant growth, development, and responses to biotic and abiotic stress. Despite the functional diversity, almost all analyzed WRKY proteins recognize the TTGACC/T W-box sequences and, therefore, mechanisms other than mere recognition of the core W-box promoter elements are necessary to achieve the regulatory specificity of WRKY transcription factors. Research over the past several years has revealed that WRKY transcription factors physically interact with a wide range of proteins with roles in signaling, transcription, and chromatin remodeling. Studies of WRKY-interacting proteins have provided important insights into the regulation and mode of action of members of the important family of transcription factors. It has also emerged that the slightly varied WRKY domains and other protein motifs conserved within each of the seven WRKY subfamilies participate in protein-protein interactions and mediate complex functional interactions between WRKY proteins and between WRKY and other regulatory proteins in the modulation of important biological processes. In this review, we summarize studies of protein-protein interactions for WRKY transcription factors and discuss how the interacting partners contribute, at different levels, to the establishment of the complex regulatory and functional network of WRKY transcription factors.

Emerging factors associated with the decline of a gray fox population and multi-scale land cover associations of mesopredators in the Chicago metropolitan area.

Energy Technology Data Exchange (ETDEWEB)

Willingham, Alison N.; /Ohio State U.

2008-01-01

mortality due to coyote predation was documented and disease was a major mortality source for foxes. The declining relative abundance of gray fox in Illinois is likely a result of a combination of factors. Assessment of habitat associations indicated that urban mesopredators, particularly coyotes and foxes, perceived the landscape as relatively homogeneous and that urban mesopredators interacted with the environment at scales larger than that accommodated by remnant habitat patches. Coyote and fox presence was found to be associated with a high degree of urban development at large and intermediate spatial scales. However, at a small spatial scale fox presence was associated with high density urban land cover whereas coyote presence was associated with urban development with increased forest cover. Urban habitats can offer a diversity of prey items and anthropogenic resources and natural land cover could offer coyotes daytime resting opportunities in urban areas where they may not be as tolerated as smaller foxes. Raccoons and opossums were found to utilize moderately developed landscapes with interspersed natural and semi-natural land covers at a large spatial scale, which may facilitate dispersal movements. At intermediate and small spatial scales, both species were found to utilize areas that were moderately developed and included forested land cover. These results indicated that raccoons and opossums used natural areas in proximity to anthropogenic resources. At a large spatial scale, skunk presence was associated with highly developed landscapes with interspersed natural and semi-natural land covers. This may indicate that skunks perceived the urban matrix as more homogeneous than raccoons or opossums. At an intermediate spatial scale skunks were associated with moderate levels of development and increased forest cover, which indicated that they might utilize natural land cover in proximity to human-dominated land cover. At the smallest spatial scale skunk presence was

Emerging Functions of Transcription Factors in Malaria Parasite

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Renu Tuteja

2011-01-01

Full Text Available Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression. Plasmodium falciparum is responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.

Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

Science.gov (United States)

Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

2013-01-01

The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

Transcription Factor Functional Protein-Protein Interactions in Plant Defense Responses

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Murilo S. Alves

2014-03-01

Full Text Available Responses to biotic stress in plants lead to dramatic reprogramming of gene expression, favoring stress responses at the expense of normal cellular functions. Transcription factors are master regulators of gene expression at the transcriptional level, and controlling the activity of these factors alters the transcriptome of the plant, leading to metabolic and phenotypic changes in response to stress. The functional analysis of interactions between transcription factors and other proteins is very important for elucidating the role of these transcriptional regulators in different signaling cascades. In this review, we present an overview of protein-protein interactions for the six major families of transcription factors involved in plant defense: basic leucine zipper containing domain proteins (bZIP, amino-acid sequence WRKYGQK (WRKY, myelocytomatosis related proteins (MYC, myeloblastosis related proteins (MYB, APETALA2/ ETHYLENE-RESPONSIVE ELEMENT BINDING FACTORS (AP2/EREBP and no apical meristem (NAM, Arabidopsis transcription activation factor (ATAF, and cup-shaped cotyledon (CUC (NAC. We describe the interaction partners of these transcription factors as molecular responses during pathogen attack and the key components of signal transduction pathways that take place during plant defense responses. These interactions determine the activation or repression of response pathways and are crucial to understanding the regulatory networks that modulate plant defense responses.

NUR TRANSCRIPTION FACTORS IN STRESS AND ADDICTION

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Danae eCampos-Melo

2013-12-01

Full Text Available The Nur transcription factors Nur77 (NGFI-B, NR4A1, Nurr1 (NR4A2 and Nor-1 (NR4A3 are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit, due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

Mycobacterium bovis Infection of Red Fox, France.

Science.gov (United States)

Michelet, Lorraine; De Cruz, Krystel; Hénault, Sylvie; Tambosco, Jennifer; Richomme, Céline; Réveillaud, Édouard; Gares, Hélène; Moyen, Jean-Louis; Boschiroli, María Laura

2018-06-01

Mycobacterium bovis infection in wild red foxes was found in southern France, where livestock and other wildlife species are infected. Foxes frequently interact with cattle but have been underestimated as a reservoir of M. bovis. Our results suggest a possible role of the red fox in the epidemiology of bovine tuberculosis.

Syntheses and Thermal Behaviors of Rb(FOX-7)·H2O and Cs(FOX-7)·H2O

International Nuclear Information System (INIS)

Luo, Jinan; Xu, Kangzhen; Wang, Min; Ren, Xiaolei; Chen, Yongshun; Song, Jirong; Zhao, Fengqi

2010-01-01

Two new energetic organic alkali metal salts, 1,1-diamino-2,2-dinitroethylene rubidium salt [Rb(FOX-7)·H 2 O] and 1,1- diamino-2,2-dinitroethylene cesium salt [Cs(FOX-7)·H 2 O], were synthesized by reacting of 1,1-diamino-2,2-dinitroethylene (FOX-7) and rubidium chloride or cesium chloride in alkali methanol aqueous solution, respectively. The thermal behaviors of Rb(FOX-7)·H 2 O and Cs(FOX-7)·H 2 O were studied with DSC and TG methods. The critical temperatures of thermal explosion of the two compounds are 216.22 and 223.73 .deg. C, respectively. Specific heat capacities of the two compounds were determined with a micro-DSC method, and the molar heat capacities are 217.46 and 199.47 J mol -1 K -1 at 298.15 K, respectively. The adiabatic times-to-explosion were also calculated to be a certain value of 5.81 - 6.36 s for Rb(FOX-7)·H 2 O, and 9.92 - 10.54 s for Cs(FOX-7)·H 2 O. After FOX-7 becoming alkali metal salts, thermal decomposition temperatures of the compounds heighten with the rise of element period, but thermal decomposition processes become intense

A case history of a dynamic resource--the red fox

Science.gov (United States)

Sargeant, A.B.; Sanderson, G.C.

1982-01-01

Red fox (Vulpes vulpes) population trends in midwestern North America since 1800 were examined. During 1801-1900, the red fox expanded its range south to include most of the region, but populations remained low in most areas. During 1901-30, it became scarce or absent in many northern areas but was common in southern areas. During 1931-45, populations in most of the region increased to high levels. From 1946 to 1980 populations remained high and westward range expansions occurred on the northern plains. Three factors appear primarily responsible for major population changes. Habitat conditions improved after settlement, but in many areas population buildup was delayed. Interspecific canid competition, especially from expanding coyote (Canis latrans) populations, held red fox populations at low levels, especially in the west. Excessive harvest for fur contributed to holding populations down in many areas, especially during the early 1900's when pelt values were exceptionally high. Major population increases during the 1930's and early 1940's coincided with declining pelt prices and resulted in widespread implementation of fox bounties. In the 1960's, bounties were gradually discontinued, pelt prices increased, and restrictions on season length and harvest methods were implemented in most states.

A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites

KAUST Repository

Kulakovskiy, Ivan V.; Belostotsky, A. A.; Kasianov, Artem S.; Esipova, Natalia G.; Medvedeva, Yulia; Eliseeva, Irina A.; Makeev, Vsevolod J.

2011-01-01

Motivation: Modern experimental methods provide substantial information on protein-DNA recognition. Studying arrangements of transcription factor binding sites (TFBSs) of interacting transcription factors (TFs) advances understanding

Isolation and culture of melanocytes from the arctic fox (Alopex lagopus

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Jiarong Bao

2015-09-01

Full Text Available Coat colour is a phenotypic marker of fur animal species, which was determined by the pigment generated from melanocytes. In this study, we developed and validated a method for isolation, purification and passage culture of melanocytes from the arctic fox (Alopex lagopus. Skin biopsies were harvested from the dorsal region of adult foxes and enzyme digestion by Dispase II. The primary culture of melanocytes from arctic fox skin was obtained by using keratinocyte serum-free medium supplemented with epidermal growth factor and bovine pituitary extract with/without phorbol- 12-myristate-13-acetate, and by carrying out a medium change strategy. After serial passages, it yielded pure population of melanocytes, which become efficient tools for investigating the function of colour genes and unraveling the process of melanin synthesis.

Factor requirements for transcription in the Archaeon Sulfolobus shibatae.

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Qureshi, S A; Bell, S D; Jackson, S P

1997-05-15

Archaea (archaebacteria) constitute a domain of life that is distinct from Bacteria (eubacteria) and Eucarya (eukaryotes). Although archaeal cells share many morphological features with eubacteria, their transcriptional apparatus is more akin to eukaryotic RNA polymerases I, II and III than it is to eubacterial transcription systems. Thus, in addition to possessing a 10 subunit RNA polymerase and a homologue of the TATA-binding protein (TBP), Archaea possess a polypeptide termed TFB that is homologous to eukaryotic TFIIB. Here, we investigate the factor requirements for transcription of several promoters of the archaeon Sulfolobus shibatae and its associated virus SSV. Through in vitro transcription and immunodepletion, we demonstrate that S. shibatae TBP, TFB and RNA polymerase are not complexed tightly with one another and that each is required for efficient transcription of all promoters tested. Furthermore, full transcription is restored by supplementing respective depleted extracts with recombinant TBP or TFB, indicating that TBP-associated factors or TFB-associated factors are not required. Indeed, gel-filtration suggests that Sulfolobus TBP and TFB are not associated stably with other proteins. Finally, all promoters analysed are transcribed accurately and efficiently in an in vitro system comprising recombinant TBP and TFB, together with essentially homogeneous preparation of RNA polymerase. Transcription in Archaea is therefore fundamentally homologous to that in eukaryotes, although factor requirements appear to be much less complex.

Transcription factor-based biosensor

Science.gov (United States)

Dietrich, Jeffrey A; Keasling, Jay D

2013-10-08

The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

Detecting Differential Transcription Factor Activity from ATAC-Seq Data

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Ignacio J. Tripodi

2018-05-01

Full Text Available Transcription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high-throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq, that the genome-wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TFs are altered by a perturbation is simple, is quick to implement, and can be used when biological samples are limited. In the future, we envision that this method could be applied to determine which TFs show altered activity in response to a wide variety of drugs and diseases.

Functional Profiling of Transcription Factor Genes in Neurospora crassa

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Alexander J. Carrillo

2017-09-01

Full Text Available Regulation of gene expression by DNA-binding transcription factors is essential for proper control of growth and development in all organisms. In this study, we annotate and characterize growth and developmental phenotypes for transcription factor genes in the model filamentous fungus Neurospora crassa. We identified 312 transcription factor genes, corresponding to 3.2% of the protein coding genes in the genome. The largest class was the fungal-specific Zn2Cys6 (C6 binuclear cluster, with 135 members, followed by the highly conserved C2H2 zinc finger group, with 61 genes. Viable knockout mutants were produced for 273 genes, and complete growth and developmental phenotypic data are available for 242 strains, with 64% possessing at least one defect. The most prominent defect observed was in growth of basal hyphae (43% of mutants analyzed, followed by asexual sporulation (38%, and the various stages of sexual development (19%. Two growth or developmental defects were observed for 21% of the mutants, while 8% were defective in all three major phenotypes tested. Analysis of available mRNA expression data for a time course of sexual development revealed mutants with sexual phenotypes that correlate with transcription factor transcript abundance in wild type. Inspection of this data also implicated cryptic roles in sexual development for several cotranscribed transcription factor genes that do not produce a phenotype when mutated.

Novel Amdovirus in Gray Foxes

Science.gov (United States)

Li, Linlin; Pesavento, Patricia A.; Woods, Leslie; Clifford, Deana L.; Luff, Jennifer; Wang, Chunlin

2011-01-01

We used viral metagenomics to identify a novel parvovirus in tissues of a gray fox (Urocyon cinereoargenteus). Nearly full genome characterization and phylogenetic analyses showed this parvovirus (provisionally named gray fox amdovirus) to be distantly related to Aleutian mink disease virus, representing the second viral species in the Amdovirus genus. PMID:22000359

Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

International Nuclear Information System (INIS)

Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

2004-01-01

The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

Physiological stress and Hendra virus in flying-foxes (Pteropus spp., Australia.

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Lee McMichael

Full Text Available Pteropid bats (flying-foxes are the natural reservoir of Hendra virus, an emergent paramyxovirus responsible for fatal infection in horses and humans in Australia. Pteropus alecto (the Black flying-fox and the paraphyletic P. conspicillatus (the Spectacled flying-fox appear to be the primary reservoir hosts. Previous studies have suggested that physiological and ecological factors may underpin infection dynamics in flying-foxes, and subsequent spillover to horses and in turn humans. We sought to examine temporal trends in urinary cortisol concentration in wild Australian flying-fox populations, to elucidate the putative relationship between Hendra virus infection and physiological stress. Pooled and individual urine samples were non-invasively collected from under roosting flying-foxes at two latitudinally disparate regions in the eastern Australian state of Queensland. Hendra virus detection, and (in individual urine samples sex and species determination were PCR-based. Urinary cortisol measurement used a validated enzyme immunoassay. We found no direct correlation between increased urinary cortisol and Hendra virus excretion, but our findings do suggest a biologically plausible association between low winter temperatures and elevated cortisol levels in P. alecto in the lower latitude Southeast Queensland roosts. We hypothesize an indirect association between low winter temperatures and increased Hendra virus infection and excretion, mediated by the physiological cost of thermoregulation. Our findings and our approach are directly relevant to elaboration of the disease ecology of Nipah virus and other emerging henipaviruses in bats. More broadly, they inform investigation of emerging disease infection dynamics across the wildlife/livestock/human interface.

Modulation of DNA binding by gene-specific transcription factors.

Science.gov (United States)

Schleif, Robert F

2013-10-01

The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

Transcriptional repression of BODENLOS by HD-ZIP transcription factor HB5 in Arabidopsis thaliana.

NARCIS (Netherlands)

Smet, De I.; Lau, S.; Ehrismann, J.S.; Axiotis, I.; Kolb, M.; Kientz, M.; Weijers, D.; Jürgens, G.

2013-01-01

In Arabidopsis thaliana, the phytohormone auxin is an important patterning agent during embryogenesis and post-embryonic development, exerting effects through transcriptional regulation. The main determinants of the transcriptional auxin response machinery are AUXIN RESPONSE FACTOR (ARF)

Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

Science.gov (United States)

Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

2018-04-17

Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

Shaggy Lame Fox Syndrome in Pribilof Island Arctic Foxes ( Alopex lagopus pribilofensis), Alaska.

Science.gov (United States)

Spraker, T R; White, P A

2017-03-01

A previously unrecognized condition is described in wild free-ranging Pribilof arctic foxes ( Alopex lagopus pribilofensis) from the Pribilof Islands, Alaska, USA. This condition is called shaggy lame fox syndrome (SLFS) denoting the primary clinical signs first observed. Criteria used to suspect SLFS on gross examination included emaciation, failure to shed winter pelage and moderate to severe polyarthritis. Criteria used to confirm SLFS histologically included polyarthritis (characterized by lymphoplasmacytic synovitis, tenosynovitis, bursitis, periosteal bony proliferation, and periarticular lymphoplasmacytic vasculitis) and systemic leukocytoclastic vasculitis. Other histological lesions often found included renal cortical infarcts, myocarditis with myocardial infarcts, lymphoplasmacytic meningitis, lymphoplasmacytic cuffing of meningeal and a few cerebral vessels, and cavitating infarcts of the brainstem and thalamus. The cause of SLFS is not known at this time; however, the gross and histological lesions suggest that the cause of SLFS may be a bacterial polyarthritis with a secondary immune-mediated vasculitis. These lesions are consistent with changes described with Erysipelothrix rhusiopathiae in domestic dogs; E. rhusiopathiae was identified from the synovial membrane of a swollen stifle joint and the kidney from one fox using real-time polymerase chain reaction and with culture from a fox that had gross and histological lesions of SLFS. Therefore, E. rhusiopathiae is a possible etiological agent for SLFS.

A critique on nuclear factor-kappa B and signal transducer and activator of transcription 3: The key transcription factors in periodontal pathogenesis

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Ranjith Ambili

2017-01-01

Full Text Available Periodontal disease is initiated by microorganisms in dental plaque, and host immunoinflammatory response to the microbial challenge helps in disease progression. Conventional periodontal therapy was mainly targeted on the elimination of microbial component. However, a better understanding of molecular aspects in host response will enable the clinicians to formulate effective host modulation therapy (HMT for the periodontal management. Inflammatory mediators were the main targets for HMT in the past. Transcription factors can regulate the production of multiple mediators simultaneously, and inhibition of these factors will be more beneficial than blocking individual molecule. Two important transcription factors implicated in chronic inflammatory diseases are nuclear factor kappa B (NF-κB and signal transducers and activators of transcription 3. The role of these factors in periodontal disease is a less explored area. This comprehensive review is aimed at unveiling the critical role of NF-κB and signal transducers and activators of transcription 3 in periodontal pathogenesis. An online search was performed using MEDLINE/PubMed database. All publications till 2016 related to NF-κB, signal transducer and activator of transcription 3 (STAT3, and inflammation were included in writing this review. A total of 27,390 references were published based on the search terms used. Out of these, 507 were related to the periodontal research published in English till 2016. Relevant papers were chosen after carefully reading the abstract. This review has attempted to comprehend the existing knowledge regarding the role of transcription factors NF-κB and STAT3 in periodontal disease. Moreover, it also provides a connecting molecular link for the periodontal medicine concept.

AMP-activated protein kinase couples 3-bromopyruvate-induced energy depletion to apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins.

Science.gov (United States)

Bodur, Cagri; Karakas, Bahriye; Timucin, Ahmet Can; Tezil, Tugsan; Basaga, Huveyda

2016-11-01

Most tumors primarily rely on glycolysis rather than mitochondrial respiration for ATP production. This phenomenon, also known as Warburg effect, renders tumors more sensitive to glycolytic disturbances compared to normal cells. 3-bromopyruvate is a potent inhibitor of glycolysis that shows promise as an anticancer drug candidate. Although investigations revealed that 3-BP triggers apoptosis through ATP depletion and subsequent AMPK activation, the underlying molecular mechanisms coupling AMPK to apoptosis are poorly understood. We showed that 3-BP leads to a rapid ATP depletion which was followed by growth inhibition and Bax-dependent apoptosis in HCT116 cells. Apoptosis was accompanied with activation of caspase-9 and -3 while pretreatment with a general caspase inhibitor attenuated cell death. AMPK, p38, JNK, and Akt were phosphorylated immediately upon treatment. Pharmacological inhibition and silencing of AMPK largely inhibited 3-BP-induced apoptosis and reversed phosphorylation of JNK. Transcriptional activity of FoxO3a was dramatically increased subsequent to AMPK-mediated phosphorylation of FoxO3a at Ser413. Cell death analysis of cells transiently transfected with wt or AMPK-phosphorylation-deficient FoxO3 expression plasmids verified the contributory role of AMPK-FoxO3a axis in 3-BP-induced apoptosis. In addition, expression of proapoptotic Bcl-2 proteins Bim and Bax were upregulated in an AMPK-dependent manner. Bim was transcriptionally activated in association with FoxO3a activity, while Bax upregulation was abolished in p53-null cells. Together, these data suggest that AMPK couples 3-BP-induced metabolic disruption to intrinsic apoptosis via modulation of FoxO3a-Bim axis and Bax expression. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile.

Science.gov (United States)

Vicario, Alba; Mendoza, Ezequiel; Abellán, Antonio; Scharff, Constance; Medina, Loreta

2017-01-01

We used a battery of genes encoding transcription factors (Pax6, Islet1, Nkx2.1, Lhx6, Lhx5, Lhx9, FoxP2) and neuropeptides to study the extended amygdala in developing zebra finches. We identified different components of the central extended amygdala comparable to those found in mice and chickens, including the intercalated amygdalar cells, the central amygdala, and the lateral bed nucleus of the stria terminalis. Many cells likely originate in the dorsal striatal domain, ventral striatal domain, or the pallidal domain, as is the case in mice and chickens. Moreover, a cell subpopulation of the central extended amygdala appears to originate in the prethalamic eminence. As a general principle, these different cells with specific genetic profiles and embryonic origin form separate or partially intermingled cell corridors along the extended amygdala, which may be involved in different functional pathways. In addition, we identified the medial amygdala of the zebra finch. Like in the chickens and mice, it is located in the subpallium and is rich in cells of pallido-preoptic origin, containing minor subpopulations of immigrant cells from the ventral pallium, alar hypothalamus and prethalamic eminence. We also proposed that the medial bed nucleus of the stria terminalis is composed of several parallel cell corridors with different genetic profile and embryonic origin: preoptic, pallidal, hypothalamic, and prethalamic. Several of these cell corridors with distinct origin express FoxP2, a transcription factor implicated in synaptic plasticity. Our results pave the way for studies using zebra finches to understand the neural basis of social behavior, in which the extended amygdala is involved.

Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.

Science.gov (United States)

Riechmann, J L; Heard, J; Martin, G; Reuber, L; Jiang, C; Keddie, J; Adam, L; Pineda, O; Ratcliffe, O J; Samaha, R R; Creelman, R; Pilgrim, M; Broun, P; Zhang, J Z; Ghandehari, D; Sherman, B K; Yu, G

2000-12-15

The completion of the Arabidopsis thaliana genome sequence allows a comparative analysis of transcriptional regulators across the three eukaryotic kingdoms. Arabidopsis dedicates over 5% of its genome to code for more than 1500 transcription factors, about 45% of which are from families specific to plants. Arabidopsis transcription factors that belong to families common to all eukaryotes do not share significant similarity with those of the other kingdoms beyond the conserved DNA binding domains, many of which have been arranged in combinations specific to each lineage. The genome-wide comparison reveals the evolutionary generation of diversity in the regulation of transcription.

BACH transcription factors in innate and adaptive immunity.

Science.gov (United States)

Igarashi, Kazuhiko; Kurosaki, Tomohiro; Roychoudhuri, Rahul

2017-07-01

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4 + regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

Thirty-seven transcription factor genes differentially respond to a ...

Indian Academy of Sciences (India)

Plant transcription factors and insect defence si. Thirty-seven transcription factor genes differentially respond to a harpin protein and affect resistance to the green peach aphid in Arabidopsis. HUNLIN. PIN. RUOXUE LIŲ, BEIBEI LÜ, XIAOMENG WANG, CHUNLING ZHANG, SHUPING ZHANG, JUN QIAN, LEI CHEN,.

Structural Fingerprints of Transcription Factor Binding Site Regions

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Peter Willett

2009-03-01

Full Text Available Fourier transforms are a powerful tool in the prediction of DNA sequence properties, such as the presence/absence of codons. We have previously compiled a database of the structural properties of all 32,896 unique DNA octamers. In this work we apply Fourier techniques to the analysis of the structural properties of human chromosomes 21 and 22 and also to three sets of transcription factor binding sites within these chromosomes. We find that, for a given structural property, the structural property power spectra of chromosomes 21 and 22 are strikingly similar. We find common peaks in their power spectra for both Sp1 and p53 transcription factor binding sites. We use the power spectra as a structural fingerprint and perform similarity searching in order to find transcription factor binding site regions. This approach provides a new strategy for searching the genome data for information. Although it is difficult to understand the relationship between specific functional properties and the set of structural parameters in our database, our structural fingerprints nevertheless provide a useful tool for searching for function information in sequence data. The power spectrum fingerprints provide a simple, fast method for comparing a set of functional sequences, in this case transcription factor binding site regions, with the sequences of whole chromosomes. On its own, the power spectrum fingerprint does not find all transcription factor binding sites in a chromosome, but the results presented here show that in combination with other approaches, this technique will improve the chances of identifying functional sequences hidden in genomic data.

FoxO/Daf-16 restored thrashing movement reduced by heat stress in Caenorhabditis elegans.

Science.gov (United States)

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2014-04-01

Many studies on thermotolerance have been done in Caenorhabditis elegans in order to extend survival under heat stress; Daf-16, a homolog of FoxO in C. elegans, was detected as the key factor in thermotolerance. However, the recovery process from heat stress damage has been seldom discussed. In this study, we analyzed the roles of FoxO/Daf-16 on the recovery from heat stress damage by monitoring thrashing movement. Heat shock reduced the movement, which was restored by culturing at 20°C. Thrashing movement was not restored in the daf-16 mutant, which suggests that Daf-16 is one of the essential factors in repairing the damage. Movement restoration was promoted in the daf-2 mutant, a homolog of insulin/IGF-1-like receptor, in a daf-16-dependent manner. In addition, heat stress decreased the expression of daf-28 and ins-7, agonists of Daf-2. Taken together, these results revealed that FoxO/Daf-16 removes heat stress damage and restores movement via inhibition of the insulin-like signaling pathway in C. elegans, suggesting that FoxO/Daf-16 plays a critical role in thermotolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular Mechanisms in the shock induced decomposition of FOX-7

Science.gov (United States)

Mishra, Ankit; Tiwari, Subodh C.; Nakano, Aiichiro; Vashishta, Priya; Kalia, Rajiv; CACS Team

Experimental and first principle computational studies on FOX 7 have either involved a very small system consisting of a few atoms or they did not take into account the decomposition mechanisms under extreme conditions of temperature and pressure. We have performed a large-scale reactive MD simulation using ReaxFF-lg force field to study the shock decomposition of FOX 7. The chemical composition of the principal decomposition products correlates well with experimental observations. Furthermore, we observed that the production of N2 and H2O was inter molecular in nature and was through different chemical pathways. Moreover, the production of CO and CO2 was delayed due to production of large stable C,O atoms cluster. These critical insights into the initial processes involved in the shock induced decomposition of FOX-7 will greatly help in understanding the factors playing an important role in the insensitiveness of this high energy material. This research is supported by AFOSR Award No. FA9550-16-1-0042.

FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc

OpenAIRE

Wang, Zheng; Fu, Changfeng; Chen, Yong; Xu, Feng; Wang, Zhenyu; Qu, Zhigang; Liu, Yi

2016-01-01

Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. Thi...

NAC Transcription Factors in Stress Responses and Senescence

DEFF Research Database (Denmark)

O'Shea, Charlotte

Plant-specific NAM/ATAF/CUC (NAC) transcription factors have recently received considerable attention due to their significant roles in plant development and stress signalling. This interest has resulted in a number of physiological, genetic and cell biological studies of their functions. Some...... of these studies have also revealed emerging gene regulatory networks and protein-protein interaction networks. However, structural studies relating structure to function are lagging behind. Structure-function analysis of the NAC transcription factors has therefore been the main focus of this PhD thesis...... not involve significant folding-upon-binding but fuzziness or an extended ANAC046 region. The ANAC046 regulatory domain functions as an entropic chain with a bait for interactions with for example RCD1. RCD1 interacts with transcription factors from several different families, and the large stress...

Cross-Family Transcription Factor Interactions

NARCIS (Netherlands)

Bemer, Marian; Dijk, van Aalt-Jan; Immink, Richard G.H.; Angenent, Gerco C.

2017-01-01

Specific and dynamic gene expression strongly depends on transcription factor (TF) activity and most plant TFs function in a combinatorial fashion. They can bind to DNA and control the expression of the corresponding gene in an additive fashion or cooperate by physical interactions, forming larger

Transcription factor interplay in T helper cell differentiation

Science.gov (United States)

Evans, Catherine M.

2013-01-01

The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity. PMID:23878131

Transcription factor interplay in T helper cell differentiation.

Science.gov (United States)

Evans, Catherine M; Jenner, Richard G

2013-11-01

The differentiation of CD4 helper T cells into specialized effector lineages has provided a powerful model for understanding immune cell differentiation. Distinct lineages have been defined by differential expression of signature cytokines and the lineage-specifying transcription factors necessary and sufficient for their production. The traditional paradigm of differentiation towards Th1 and Th2 subtypes driven by T-bet and GATA3, respectively, has been extended to incorporate additional T cell lineages and transcriptional regulators. Technological advances have expanded our view of these lineage-specifying transcription factors to the whole genome and revealed unexpected interplay between them. From these data, it is becoming clear that lineage specification is more complex and plastic than previous models might have suggested. Here, we present an overview of the different forms of transcription factor interplay that have been identified and how T cell phenotypes arise as a product of this interplay within complex regulatory networks. We also suggest experimental strategies that will provide further insight into the mechanisms that underlie T cell lineage specification and plasticity.

Members of FOX family could be drug targets of cancers.

Science.gov (United States)

Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua

2018-01-01

FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.

Fox-7 for Insensitive Boosters

Science.gov (United States)

2010-08-01

cavitation , and therefore nucleation, to occur at each frequency. As well as producing ultrasound at different frequencies, the method of delivery of...processing techniques using ultrasound , designed to optimise FOX-7 crystal size and morphology to improve booster formulations, and results from these...7 booster formulations. Also included are particle processing techniques using ultrasound , designed to optimise FOX-7 crystal size and morphology

Enhanceosomes as integrators of hypoxia inducible factor (HIF) and other transcription factors in the hypoxic transcriptional response.

Science.gov (United States)

Pawlus, Matthew R; Hu, Cheng-Jun

2013-09-01

Hypoxia is a prevalent attribute of the solid tumor microenvironment that promotes the expression of genes through posttranslational modifications and stabilization of alpha subunits (HIF1α and HIF2α) of hypoxia-inducible factors (HIFs). Despite significant similarities, HIF1 (HIF1α/ARNT) and HIF2 (HIF2α/ARNT) activate common as well as unique target genes and exhibit different functions in cancer biology. More surprisingly, accumulating data indicates that the HIF1- and/or HIF2-mediated hypoxia responses can be oncogenic as well as tumor suppressive. While the role of HIF in the hypoxia response is well established, recent data support the concept that HIF is necessary, but not sufficient for the hypoxic response. Other transcription factors that are activated by hypoxia are also required for the HIF-mediated hypoxia response. HIFs, other transcription factors, co-factors and RNA poll II recruited by HIF and other transcription factors form multifactorial enhanceosome complexes on the promoters of HIF target genes to activate hypoxia inducible genes. Importantly, HIF1 or HIF2 requires distinct partners in activating HIF1 or HIF2 target genes. Because HIF enhanceosome formation is required for the gene activation and distinct functions of HIF1 and HIF2 in tumor biology, disruption of the HIF1 or HIF2 specific enhanceosome complex may prove to be a beneficial strategy in tumor treatment in which tumor growth is specifically dependent upon HIF1 or HIF2 activity. Copyright © 2013 Elsevier Inc. All rights reserved.

DNA Binding by the Ribosomal DNA Transcription Factor Rrn3 Is Essential for Ribosomal DNA Transcription*

Science.gov (United States)

Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H.; Rothblum, Katrina; Schneider, David A.; Rothblum, Lawrence I.

2013-01-01

The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382–400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I. PMID:23393135

DNA binding by the ribosomal DNA transcription factor rrn3 is essential for ribosomal DNA transcription.

Science.gov (United States)

Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H; Rothblum, Katrina; Schneider, David A; Rothblum, Lawrence I

2013-03-29

The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382-400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I.

Diets of swift foxes (Vulpes velox) in continuous and fragmented prairie in Northwestern Texas

Science.gov (United States)

Kamler, J.F.; Ballard, W.B.; Wallace, M.C.; Gipson, P.S.

2007-01-01

Distribution of the swift fox (Vulpes velox) has declined dramatically since the 1800s, and suggested causes of this decline are habitat fragmentation and transformation due to agricultural expansion. However, impacts of fragmentation and human-altered habitats on swift foxes still are not well understood. To better understand what effects these factors have on diets of swift foxes, scats were collected in northwestern Texas at two study sites, one of continuous native prairie and one representing fragmented native prairie interspersed with agricultural and fields in the Conservation Reserve Program. Leporids, a potential food source, were surveyed seasonally on both sites. Diets of swift foxes differed between sites; insects were consumed more on continuous prairie, whereas mammals, birds, and crops were consumed more on fragmented prairie. Size of populations of leporids were 2-3 times higher on fragmented prairie, and swift foxes responded by consuming more leporids on fragmented (11.1% frequency occurrence) than continuous (3.8%) prairie. Dietary diversity was greater on fragmented prairie during both years of the study. Differences in diets between sites suggested that the swift fox is an adaptable and opportunistic feeder, able to exploit a variety of food resources, probably in relation to availability of food. We suggest that compared to continuous native prairie, fragmented prairie can offer swift foxes a more diverse prey base, at least within the mosaic of native prairie, agricultural, and fields that are in the Conservation Reserve Program.

Comparison of selected immunological parameters in silver and polar foxes

International Nuclear Information System (INIS)

Kostro, K.; Woloszyn, S.

1996-01-01

The aim of the work was to compare selected nonspecific immunological parameters in silver and polar foxes. It was found that out of three mitogens (Con A, La and PWM) only Con A stimulated the strongest lymphocyte proliferation in both species of foxes. Mean stimulation indices and the absolute values of incorporated thymidine were significantly higher in polar foxes. The average percentages of phagocytes and the fatal indices of neutrophils were comparable in both species of foxes, while the mean value of the phagocyte index was much higher in the silver fox. However, in polar foxes a higher concentration of lysozyme in the blood serum was found. The differences in the parameters may influence the susceptibility of these foxes to some infections already at the level of nonspecific primary response. (author)

Spatial relations between sympatric coyotes and red foxes in North Dakota

Science.gov (United States)

Sargeant, A.B.; Allen, S.H.; Hastings, J.O.

1987-01-01

Spatial relations between coyotes (Canis latrans) and red foxes (Vulpes vulpes) on a 360-km2 area in North Dakota were studied during 1977-78. Coyote families occupied large (mean = 61.2 km2), relatively exclusive territories that encompassed about one-half of the study area. Fox families occupied much smaller (mean = 11.9 km2), relatively exclusive, territories that overlapped perimeters of coyote territories and/or encompassed area unoccupied by coyotes. No fox family lived totally within a coyote territory, but 3 fox families lived within the 153.6-km2 home range of an unattached yearling male coyote. Both coyotes and foxes, from families with overlapping territories, tended to use their overlap areas less than was expected by amount of overlap. Encounters between radio-equipped coyotes and foxes from families with overlapping territories occurred less often than was expected by chance. Foxes living near coyotes exhibited considerable tenacity to their territories, and no monitored fox was killed by coyotes during 2,518 fox-days of radio surveillance. A hypothesis for coyote-induced fox population declines, based largely on fox avoidance mechanisms, is presented.

TrSDB: a proteome database of transcription factors

Science.gov (United States)

Hermoso, Antoni; Aguilar, Daniel; Aviles, Francesc X.; Querol, Enrique

2004-01-01

TrSDB—TranScout Database—(http://ibb.uab.es/trsdb) is a proteome database of eukaryotic transcription factors based upon predicted motifs by TranScout and data sources such as InterPro and Gene Ontology Annotation. Nine eukaryotic proteomes are included in the current version. Extensive and diverse information for each database entry, different analyses considering TranScout classification and similarity relationships are offered for research on transcription factors or gene expression. PMID:14681387

Genetic characteristics of red foxes In northeastern Oregon

Science.gov (United States)

Gregory A Green; Benjamin N Sacks; Leonard J Erickson; Keith B Aubry

2017-01-01

The Rocky Mountain Red Fox (Vulpes vulpes macroura), once common in the Blue Mountains ecoregion of northeastern Oregon, was considered rare in eastern Oregon by the 1930s and thought to be extirpated by the 1960s, when putatively new Red Fox populations began to appear. Although the new foxes were long presumed to be nonnative (originating from...

Examination of D. immitis presence in foxes in Serbia

Directory of Open Access Journals (Sweden)

Gavrilović Pavle

2014-01-01

Full Text Available Dirofilariosis is a parasitic disease that usually affects dogs, but it can occur in other carnivore species. Since the disease appears endemically in dogs in some parts of Serbia, the aim of our investigation was to determine whether dirofilariosis exists in wild animals. The study included a total of 150 red foxes (Vulpes vulpes, 30 hunted foxes per region of South Banat, Raska, Rasina, Morava and Zlatibor were examined. After the corpses of foxes were autopsied, the heart and blood vessels were examined macroscopically for the evidence of adult forms of D. immitis. The presence of the agent was found in four foxes from the territory of three municipalities of South Banat: Kovin, Alibunar and Opovo, representing 13.33% of the total number of examined foxes in this region. None of the 120 autopsied foxes from four districts of central Serbia was found to have dirofilaria. The results obtained in investigation lead to conclusion that dirofilariosis exists as a parasitic disease in red foxes in South Banat.

Using TESS to predict transcription factor binding sites in DNA sequence.

Science.gov (United States)

Schug, Jonathan

2008-03-01

This unit describes how to use the Transcription Element Search System (TESS). This Web site predicts transcription factor binding sites (TFBS) in DNA sequence using two different kinds of models of sites, strings and positional weight matrices. The binding of transcription factors to DNA is a major part of the control of gene expression. Transcription factors exhibit sequence-specific binding; they form stronger bonds to some DNA sequences than to others. Identification of a good binding site in the promoter for a gene suggests the possibility that the corresponding factor may play a role in the regulation of that gene. However, the sequences transcription factors recognize are typically short and allow for some amount of mismatch. Because of this, binding sites for a factor can typically be found at random every few hundred to a thousand base pairs. TESS has features to help sort through and evaluate the significance of predicted sites.

Microarray-Based Identification of Transcription Factor Target Genes

NARCIS (Netherlands)

Gorte, M.; Horstman, A.; Page, R.B.; Heidstra, R.; Stromberg, A.; Boutilier, K.A.

2011-01-01

Microarray analysis is widely used to identify transcriptional changes associated with genetic perturbation or signaling events. Here we describe its application in the identification of plant transcription factor target genes with emphasis on the design of suitable DNA constructs for controlling TF

Repression of meiotic genes by antisense transcription and by Fkh2 transcription factor in Schizosaccharomyces pombe.

Science.gov (United States)

Chen, Huei-Mei; Rosebrock, Adam P; Khan, Sohail R; Futcher, Bruce; Leatherwood, Janet K

2012-01-01

In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s) of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the "unspliced" signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression.

Michael J. Fox: Spurring Research on Parkinson's

Science.gov (United States)

... turn JavaScript on. Feature: Parkinson's Disease Michael J. Fox: Spurring Research on Parkinson's Past Issues / Winter 2014 Table of Contents Michael J. Fox and his wife, actress Tracy Pollan, founded the ...

33 CFR 117.1087 - Fox River.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Fox River. 117.1087 Section 117.1087 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Wisconsin § 117.1087 Fox River. (a) The draws of the Canadian...

Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice*

Science.gov (United States)

Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M.; Piganelli, Jon D.; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H. Henry

2015-01-01

Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. PMID:25944898

Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors.

Science.gov (United States)

Narasimhan, Kamesh; Micoine, Kevin; Lacôte, Emmanuel; Thorimbert, Serge; Cheung, Edwin; Hasenknopf, Bernold; Jauch, Ralf

2014-01-01

SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology. However, rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology. Polyoxometalates (POMs) are inorganic compounds that were previously shown to target the high-mobility group (HMG) of SOX proteins at nanomolar concentrations. In continuation of this work, we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs. The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates. Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class. Further, organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity. The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency. Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures

TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions

KAUST Repository

Schmeier, Sebastian; Alam, Tanvir; Essack, Magbubah; Bajic, Vladimir B.

2016-01-01

Transcription factors (TFs) play a pivotal role in transcriptional regulation, making them crucial for cell survival and important biological functions. For the regulation of transcription, interactions of different regulatory proteins known as transcription co-factors (TcoFs) and TFs are essential in forming necessary protein complexes. Although TcoFs themselves do not bind DNA directly, their influence on transcriptional regulation and initiation, although indirect, has been shown to be significant, with the functionality of TFs strongly influenced by the presence of TcoFs. In the TcoF-DB v2 database, we collect information on TcoFs. In this article, we describe updates and improvements implemented in TcoF-DB v2. TcoF-DB v2 provides several new features that enables exploration of the roles of TcoFs. The content of the database has significantly expanded, and is enriched with information from Gene Ontology, biological pathways, diseases and molecular signatures. TcoF-DB v2 now includes many more TFs; has substantially increased the number of human TcoFs to 958, and now includes information on mouse (418 new TcoFs). TcoF-DB v2 enables the exploration of information on TcoFs and allows investigations into their influence on transcriptional regulation in humans and mice. TcoF-DB v2 can be accessed at http://tcofdb.org/.

TcoF-DB v2: update of the database of human and mouse transcription co-factors and transcription factor interactions

KAUST Repository

Schmeier, Sebastian

2016-10-17

Transcription factors (TFs) play a pivotal role in transcriptional regulation, making them crucial for cell survival and important biological functions. For the regulation of transcription, interactions of different regulatory proteins known as transcription co-factors (TcoFs) and TFs are essential in forming necessary protein complexes. Although TcoFs themselves do not bind DNA directly, their influence on transcriptional regulation and initiation, although indirect, has been shown to be significant, with the functionality of TFs strongly influenced by the presence of TcoFs. In the TcoF-DB v2 database, we collect information on TcoFs. In this article, we describe updates and improvements implemented in TcoF-DB v2. TcoF-DB v2 provides several new features that enables exploration of the roles of TcoFs. The content of the database has significantly expanded, and is enriched with information from Gene Ontology, biological pathways, diseases and molecular signatures. TcoF-DB v2 now includes many more TFs; has substantially increased the number of human TcoFs to 958, and now includes information on mouse (418 new TcoFs). TcoF-DB v2 enables the exploration of information on TcoFs and allows investigations into their influence on transcriptional regulation in humans and mice. TcoF-DB v2 can be accessed at http://tcofdb.org/.

Pulses of movement across the sea ice: population connectivity and temporal genetic structure in the arctic fox.

Science.gov (United States)

Norén, Karin; Carmichael, Lindsey; Fuglei, Eva; Eide, Nina E; Hersteinsson, Pall; Angerbjörn, Anders

2011-08-01

Lemmings are involved in several important functions in the Arctic ecosystem. The Arctic fox (Vulpes lagopus) can be divided into two discrete ecotypes: "lemming foxes" and "coastal foxes". Crashes in lemming abundance can result in pulses of "lemming fox" movement across the Arctic sea ice and immigration into coastal habitats in search for food. These pulses can influence the genetic structure of the receiving population. We have tested the impact of immigration on the genetic structure of the "coastal fox" population in Svalbard by recording microsatellite variation in seven loci for 162 Arctic foxes sampled during the summer and winter over a 5-year period. Genetic heterogeneity and temporal genetic shifts, as inferred by STRUCTURE simulations and deviations from Hardy-Weinberg proportions, respectively, were recorded. Maximum likelihood estimates of movement as well as STRUCTURE simulations suggested that both immigration and genetic mixture are higher in Svalbard than in the neighbouring "lemming fox" populations. The STRUCTURE simulations and AMOVA revealed there are differences in genetic composition of the population between summer and winter seasons, indicating that immigrants are not present in the reproductive portion of the Svalbard population. Based on these results, we conclude that Arctic fox population structure varies with time and is influenced by immigration from neighbouring populations. The lemming cycle is likely an important factor shaping Arctic fox movement across sea ice and the subsequent population genetic structure, but is also likely to influence local adaptation to the coastal habitat and the prevalence of diseases.

Flow cytometric immunophenotyping of regulatory T cells in chronic lymphocytic leukemia: comparative assessment of various markers and use of novel antibody panel with CD127 as alternative to transcription factor FoxP3.

Science.gov (United States)

Dasgupta, Alakananda; Mahapatra, Manoranjan; Saxena, Renu

2013-04-01

This study analyzed the frequency of regulatory T cells (Tregs) in chronic lymphocytic leukemia (CLL) by multiparameter flow cytometric immunophenotyping. Patients showed significantly increased frequencies of Tregs as compared to controls, a significantly higher percentage than that identified by previous studies, possibly indicating a different prognosis of CLL in different parts of the world and, more precisely, a worse prognosis of CLL in the Indian population. A higher frequency of Tregs was also seen in advanced stage of disease with significantly reduced frequencies of Tregs in patients with CLL after chemotherapy. A significant proportion of CD127low/-FoxP3+ Tregs expressed only low levels of CD25. Thus, CD127 appears to be a better marker than CD25 for the identification of CD4+FoxP3+ T cells as potential Tregs. Our results suggest that the specificity and sensitivity of CD4+CD127low/- cells are comparable to those of CD4+FoxP3+, which is the gold standard, and can be used as an alternative. This novel flow cytometric antibody panel with fewer number of antibodies is cost-effective and can be used to enumerate Tregs in resource-limited settings.

Demonstrating Interactions of Transcription Factors with DNA by Electrophoretic Mobility Shift Assay.

Science.gov (United States)

Yousaf, Nasim; Gould, David

2017-01-01

Confirming the binding of a transcription factor with a particular DNA sequence may be important in characterizing interactions with a synthetic promoter. Electrophoretic mobility shift assay is a powerful approach to demonstrate the specific DNA sequence that is bound by a transcription factor and also to confirm the specific transcription factor involved in the interaction. In this chapter we describe a method we have successfully used to demonstrate interactions of endogenous transcription factors with sequences derived from endogenous and synthetic promoters.

What does the fox say? Monitoring antimicrobial resistance in the environment using wild red foxes as an indicator.

Directory of Open Access Journals (Sweden)

Solveig Sølverød Mo

Full Text Available The objective of this study was to estimate and compare the occurrence of AMR in wild red foxes in relation to human population densities. Samples from wild red foxes (n = 528 included in the Norwegian monitoring programme on antimicrobial resistance in bacteria from food, feed and animals were included. All samples were divided into three different groups based on population density in the municipality where the foxes were hunted. Of the 528 samples included, 108 (20.5%, 328 (62.1% and 92 (17.4% originated from areas with low, medium and high population density, respectively. A single faecal swab was collected from each fox. All samples were plated out on a selective medium for Enterobacteriaceae for culturing followed by inclusion and susceptibility testing of one randomly selected Escherichia coli to assess the overall occurrence of AMR in the Gram-negative bacterial population. Furthermore, the samples were subjected to selective screening for detection of E. coli displaying resistance towards extended-spectrum cephalosporins and fluoroquinolones. In addition, a subset of samples (n = 387 were subjected to selective culturing to detect E. coli resistant to carbapenems and colistin, and enterococci resistant to vancomycin. Of these, 98 (25.3%, 200 (51.7% and 89 (23.0% originated from areas with low, medium and high population density, respectively. Overall, the occurrence of AMR in indicator E. coli from wild red foxes originating from areas with different human population densities in Norway was low to moderate (8.8%. The total occurrence of AMR was significantly higher; χ2 (1,N = 336 = 6.53, p = 0.01 in areas with high population density compared to areas with medium population density. Similarly, the occurrence of fluoroquinolone resistant E. coli isolated using selective detection methods was low in areas with low population density and more common in areas with medium or high population density. In conclusion, we found indications that

Rough-legged buzzards, Arctic foxes and red foxes in a tundra ecosystem without rodents.

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Ivan Pokrovsky

Full Text Available Small rodents with multi-annual population cycles strongly influence the dynamics of food webs, and in particular predator-prey interactions, across most of the tundra biome. Rodents are however absent from some arctic islands, and studies on performance of arctic predators under such circumstances may be very instructive since rodent cycles have been predicted to collapse in a warming Arctic. Here we document for the first time how three normally rodent-dependent predator species-rough-legged buzzard, arctic fox and red fox - perform in a low-arctic ecosystem with no rodents. During six years (in 2006-2008 and 2011-2013 we studied diet and breeding performance of these predators in the rodent-free Kolguev Island in Arctic Russia. The rough-legged buzzards, previously known to be a small rodent specialist, have only during the last two decades become established on Kolguev Island. The buzzards successfully breed on the island at stable low density, but with high productivity based on goslings and willow ptarmigan as their main prey - altogether representing a novel ecological situation for this species. Breeding density of arctic fox varied from year to year, but with stable productivity based on mainly geese as prey. The density dynamic of the arctic fox appeared to be correlated with the date of spring arrival of the geese. Red foxes breed regularly on the island but in very low numbers that appear to have been unchanged over a long period - a situation that resemble what has been recently documented from Arctic America. Our study suggests that the three predators found breeding on Kolguev Island possess capacities for shifting to changing circumstances in low-arctic ecosystem as long as other small - medium sized terrestrial herbivores are present in good numbers.

Systemic AA amyloidosis in the red fox (Vulpes vulpes).

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Rising, Anna; Cederlund, Ella; Palmberg, Carina; Uhlhorn, Henrik; Gaunitz, Stefan; Nordling, Kerstin; Ågren, Erik; Ihse, Elisabet; Westermark, Gunilla T; Tjernberg, Lars; Jörnvall, Hans; Johansson, Jan; Westermark, Per

2017-11-01

Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model. © 2017 The Protein Society.

Repression of Meiotic Genes by Antisense Transcription and by Fkh2 Transcription Factor in Schizosaccharomyces pombe

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Chen, Huei-Mei; Rosebrock, Adam P.; Khan, Sohail R.; Futcher, Bruce; Leatherwood, Janet K.

2012-01-01

In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s) of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the “unspliced” signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression. PMID:22238674

Repression of meiotic genes by antisense transcription and by Fkh2 transcription factor in Schizosaccharomyces pombe.

Directory of Open Access Journals (Sweden)

Huei-Mei Chen

Full Text Available In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the "unspliced" signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression.

Winter activity of bat-eared foxes Otocyon megalotis on the Cape ...

African Journals Online (AJOL)

Diurnal activity budgets of bat-eared foxes Otocyon megalotis in winter (June) at the Postberg Nature Reserve, West Coast National Park, were analysed to determine the influence of environmental factors on their activity. Abiotic factors such as effective temperature, wind speed, cloud cover and rainfall have an effect on ...

DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation

OpenAIRE

Alexandrov, Boian S.; Gelev, Vladimir; Yoo, Sang Wook; Alexandrov, Ludmil B.; Fukuyo, Yayoi; Bishop, Alan R.; Rasmussen, Kim ?.; Usheva, Anny

2009-01-01

We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results demonstrate that DNA dynamic activity at the TSS can be suppressed by mutations that do not affect basal transcription factor binding–DNA co...

The logic of communication: roles for mobile transcription factors in plants.

Science.gov (United States)

Long, Yuchen; Scheres, Ben; Blilou, Ikram

2015-02-01

Mobile transcription factors play many roles in plant development. Here, we compare the use of mobile transcription factors as signals with some canonical signal transduction processes in prokaryotes and eukaryotes. After an initial survey, we focus on the SHORT-ROOT pathway in Arabidopsis roots to show that, despite the simplicity of the concept of mobile transcription factor signalling, many lines of evidence reveal a surprising complexity in control mechanisms linked to this process. We argue that these controls bestow precision, robustness, and versatility on mobile transcription factor signalling. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Environmental conditions predict helminth prevalence in red foxes in Western Australia☆

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Dybing, Narelle A.; Fleming, Patricia A.; Adams, Peter J.

2013-01-01

Red foxes (Vulpes vulpes) are the most common and widely distributed wild carnivore worldwide. These predators harbour a wide range of parasites, many of which may have important conservation, agricultural and zoonotic repercussions. This project investigated the occurrence of helminth parasites from the intestines of 147 red foxes across 14 sampling localities of southwest Western Australia. Helminth parasites were detected in 58% of fox intestines: Dipylidium caninum (27.7% of foxes), Uncinaria stenocephala (18.2%), Toxocara canis (14.9%), Spirometra erinaceieuropaei (5.4%), Toxascaris leonina (4.7%), Taenia serialis (1.4%), Taenia hydatigena (0.7%), unidentified Taenia spp. (4.1%), Brachylaima cribbi (0.7%), Plagiorchis maculosus (0.7%) and an Acanthocephalan; family Centrorhynchidae (2.1%). Importantly, two cestodes of agricultural significance, Echinococcus granulosus and Taenia ovis, were not detected in red foxes in this study, despite the presence of suitable intermediate hosts in the diets of these animals. Parasite richness varied from 1–3 species per host, with average parasite number varying from 1–39 worms (across all helminth species). Regression analyses indicated that the presence of four helminth parasites was related to various environmental factors. The presence of S. erinaceieuropaei (p < 0.001), T. leonina (p < 0.01) and U. stenocephala (p < 0.01) was positively associated with average relative humidity which may affect the longevity of infective stages in the environment. The presence of S. erinaceieuropaei and U. stenocephala (p < 0.001) was positively associated with 5-y-average minimum temperature which could reflect poor survival of infective stages through cold winter conditions. The presence of T. canis and U. stenocephala (p < 0.001) was positively associated with the percentage cover of native vegetation at each sampling location, which is likely to reflect transmission from native prey species acting as paratenic hosts

Transcription factor NF-kB as a potential biomarker for oxidative stress

NARCIS (Netherlands)

Berg, R. van den; Haenen, G.R.M.M.; Berg, H. van den; Bast, A.

2001-01-01

There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-κB (nuclear factor-κB), in the pathogenesis of various diseases. NF-κB is involved in the control of the transcription of a variety of cellular genes that regulate the inflammatory

Specific detection of Echinococcus spp. from the Tibetan fox (Vulpes ferrilata) and the red fox (V. vulpes) using copro-DNA PCR analysis.

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Jiang, Weibin; Liu, Nan; Zhang, Gaotian; Renqing, Pengcuo; Xie, Fei; Li, Tiaoying; Wang, Zhenghuan; Wang, Xiaoming

2012-10-01

There are three Echinococcus species, Echinococcus granulosus, E. multilocularis, and E. shiquicus, which are distributed on the vast area of pastureland on the eastern Tibetan plateau in China. Tibetan foxes (Vulpes ferrilata) have been determined to be the main wild definitive host of E. multilocularis and E. shiquicus, but little information is available on the prevalence of these two parasites in Tibetan foxes. Consequently, the copro-prevalence of these parasites in foxes from the eastern Tibetan plateau was evaluated in this study. For each copro-DNA sample extracted from fox feces, a 133-bp segment of EgG1 Hae III was used to screen for infection with E. granulosus. Multiplex nested polymerase chain reaction (PCR) analysis was used to target an 874-bp segment of the mitochondrial COI gene to distinguish E. multilocularis and E. shiquicus. Among 184 fecal samples, 120 were from Tibetan foxes and six from red foxes (Vulpes vulpes). Of the fecal samples from Tibetan foxes, 74 (giving a copro-prevalence of 62%) showed the presence of Echinococcus spp.: 23 (19%) were found to contain E. multilocularis, 32 (27%) E. shiquicus, and 19 (16%) showed mixed infection with both E. multilocularis and E. shiquicus. Two fecal samples from red foxes were found to be infected with E. multilocularis. No fox feces were found to be infected with E. granulosus. Tests on zinc finger protein genes and a 105-bp fragment of the Sry gene found no significant difference in the prevalence of the two parasites between sexes. The efficiency of our multiplex nested PCR methods were compared with previous polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods and some problems associated with the copro-PCR were discussed.

A Multiplex PCR assay to differentiate between dog and red fox.

Science.gov (United States)

Weissenberger, M; Reichert, W; Mattern, R

2011-11-01

Foxes are frequently the cause of car accidents in Baden-Württemberg (BW, Germany). The domestic dog (Canis familiaris) is in close relation to the red fox (Vulpes vulpes) and the silver fox which is a coat colour variant of the red fox. As insurance claims that involve accidents with animals require authentication, we analyzed frequency distribution and allele sizes in two canine microsatellite loci in 26 dogs (different breeds) and 19 red foxes of the region of BW, Germany. Moreover, sequencing analysis was performed. Red foxes exhibited only 1 allele at each microsatellite locus, whereas in dog 7 alleles at the CPH4 locus and 6 alleles at the CPH12 locus were detected. Sequences of PCR products from the two species revealed several differences between dogs and foxes. We established a sequenced allelic ladder and give population data from dogs and red foxes from the region of BW, Germany. Using microsatellite polymorphisms is efficient in differentiating between dogs and foxes in forensic casework. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice.

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Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M; Piganelli, Jon D; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H Henry

2015-06-19

Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Transcription factor binding sites prediction based on modified nucleosomes.

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Mohammad Talebzadeh

Full Text Available In computational methods, position weight matrices (PWMs are commonly applied for transcription factor binding site (TFBS prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method

Where to deliver baits for deworming urban red foxes for Echinococcus multilocularis control: new protocol for micro-habitat modeling of fox denning requirements.

Science.gov (United States)

Ikeda, Takako; Yoshimura, Masashi; Onoyama, Keiichi; Oku, Yuzaburo; Nonaka, Nariaki; Katakura, Ken

2014-08-06

Deworming wild foxes by baiting with the anthelmintic praziquantel is being established as a preventive technique against environmental contamination with Echinococcus multilocularis eggs. Improvement of the cost-benefit performance of baiting treatment is required urgently to raise and maintain the efficacy of deworming. We established a spatial model of den site selection by urban red foxes, the definitive host, to specify the optimal micro-habitats for delivering baits in a new modeling approach modified for urban fox populations. The model was established for two cities (Obihiro and Sapporo) in Hokkaido, Japan, in which a sylvatic cycle of E. multilocularis is maintained. The two cities have different degrees of urbanization. The modeling process was designed to detect the best combination of key environmental factors and spatial scale that foxes pay attention to most (here named 'heeding range') when they select den sites. All possible models were generated using logistic regression analysis, with "presence" or "absence" of fox den as the objective variable, and nine landscape categories customized for urban environments as predictor variables to detect the best subset of predictors. This procedure was conducted for each of ten sizes of concentric circles from dens and control points to detect the best circle size. Out of all models generated, the most parsimonious model was selected using Akaike's Information Criterion (AIC) inspection. Our models suggest that fox dens in Obihiro are located at the center of a circle with 500 m radius including low percentages of wide roads, narrow roads, and occupied buildings, but high percentages of green covered areas; the dens in Sapporo within 300 m radius with low percentages of wide roads, occupied buildings, but high percentages of riverbeds and green covered areas. The variation of the models suggests the necessity of accumulating models for various types of cities in order to reveal the patterns of the model. Our

Genome Binding and Gene Regulation by Stem Cell Transcription Factors

NARCIS (Netherlands)

J.H. Brandsma (Johan)

2016-01-01

markdownabstractNearly all cells of an individual organism contain the same genome. However, each cell type transcribes a different set of genes due to the presence of different sets of cell type-specific transcription factors. Such transcription factors bind to regulatory regions such as promoters

Trichinella infections in arctic foxes from Greenland

DEFF Research Database (Denmark)

Kapel, C. M O; Henriksen, S. A.; Berg, T. B.

1995-01-01

Studies were carried out to determine the predilection sites of Trichinella nativa muscle larvae in arctic foxes (Alopex lagopus) caught in Greenland. The highest number of larvae per gram of tissue was found in the muscles of the eyes and the legs. With regard to predilection sites no significant...... differences were demonstrated either between age groups or between foxes with high and low total parasite burdens. Predilection sites were comparable with those recorded earlier in experimentally infected caged foxes and in other carnivorous species. Hypotheses on predilection sites of Trichinella muscle...

Modulation of transcription factors by curcumin.

Science.gov (United States)

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

Membrane-bound transcription factors: regulated release by RIP or RUP.

Science.gov (United States)

Hoppe, T; Rape, M; Jentsch, S

2001-06-01

Regulated nuclear transport of transcription factors from cytoplasmic pools is a major route by which eukaryotes control gene expression. Exquisite examples are transcription factors that are kept in a dormant state in the cytosol by membrane anchors; such proteins are released from membranes by proteolytic cleavage, which enables these transcription factors to enter the nucleus. Cleavage can be mediated either by regulated intramembrane proteolysis (RIP) catalysed by specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent processing (RUP). In both cases processing can be controlled by cues that originate at or in the vicinity of the membrane.

Transcription Factors in Heart: Promising Therapeutic Targets in Cardiac Hypertrophy

OpenAIRE

Kohli, Shrey; Ahuja, Suchit; Rani, Vibha

2011-01-01

Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and anti-hypertrophic factors. Thi...

Hydrogen peroxide sensing, signaling and regulation of transcription factors

Directory of Open Access Journals (Sweden)

H. Susana Marinho

2014-01-01

Full Text Available The regulatory mechanisms by which hydrogen peroxide (H2O2 modulates the activity of transcription factors in bacteria (OxyR and PerR, lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4 and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1 are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1 synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M−1 s−1 and ≥1.3 × 103 M−1 s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for

Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

DEFF Research Database (Denmark)

Siersbæk, Rasmus; Rabiee, Atefeh; Nielsen, Ronni

2014-01-01

. Using a combination of advanced proteomics and genomics approaches, we identify ∼12,000 transcription factor hotspots (∼400 bp) in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate that hotspots...

Regulation of the yeast metabolic cycle by transcription factors with periodic activities

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Pellegrini Matteo

2011-10-01

Full Text Available Abstract Background When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can also be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Knowing the transcription factors involved in the yeast metabolic cycle is helpful for determining the cascade of regulatory events that cause these patterns. Results Transcription factor activities were estimated by linear regression using time series and genome-wide transcription factor binding data. Time-translation matrices were estimated using least squares and were used to model the interactions between the most significant transcription factors. The top transcription factors have functions involving respiration, cell cycle events, amino acid metabolism and glycolysis. Key regulators of transitions between phases of the yeast metabolic cycle appear to be Hap1, Hap4, Gcn4, Msn4, Swi6 and Adr1. Conclusions Analysis of the phases at which transcription factor activities peak supports previous findings suggesting that the various cellular functions occur during specific phases of the yeast metabolic cycle.

Éloge to Robert Fox

Directory of Open Access Journals (Sweden)

Efthymios Nicolaidis

2017-12-01

Full Text Available The 20th Alexandre Koyré Medal awarded since 1968 to prominent historians of science was awarded to Robert Fox, leading historian of European science of the period from the 18th to the beginnings of the 20th century. The Medal was presented to Robert Fox during the 7th International Conference of the European Society for the History of Science, Prague, 23 September 2016, and the Éloge describes his career and work.

Regulation of cell proliferation by the E2F transcription factors

DEFF Research Database (Denmark)

Helin, K

1998-01-01

Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice h......Fs in the proteasomes. Novel target genes for the E2F transcription factors have been identified that link the E2Fs directly to the initiation of DNA replication.......Experimental data generated in the past year have further emphasized the essential role for the E2F transcription factors in the regulation of cell proliferation. Genetic studies have shown that E2F activity is required for normal development in fruitflies, and the generation of E2F-1(-/-) mice has...... demonstrated that individual members of the E2F transcription factor family are likely to have distinct roles in mammalian development and homeostasis. Additional mechanisms regulating the activity of the E2F transcription factors have been reported, including subcellular localization and proteolysis of the E2...

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Science.gov (United States)

In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

1997-03-01

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Directional preference may enhance hunting accuracy in foraging foxes

Czech Academy of Sciences Publication Activity Database

Červený, J.; Begall, S.; Koubek, Petr; Nováková, P.; Burda, H.

2011-01-01

Roč. 7, č. 3 (2011), s. 355-357 ISSN 1744-9561 R&D Projects: GA ČR GA524/06/0687; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : fox * hunting behaviour * magnetoreception * magnetic alignment Subject RIV: GK - Forestry Impact factor: 3.762, year: 2011

Cs-137 in Arctic foxes (Alopex lagopus) on Svalbard

International Nuclear Information System (INIS)

Gwynn, Justin P.; Fuglei, Eva; Dowdall, Mark

2007-01-01

This study presents 137 Cs muscle activity concentrations in Arctic foxes (Alopex lagopus) from Svalbard over a period of several years and discusses the transfer of 137 Cs to Arctic foxes through likely predator-prey relationships. Mean 137 Cs activity concentrations and 137 Cs T ag values (per trapping season) ranged from 0.51 ± 2.76 to 1.32 ± 2.89 Bq/kg (w.w.) and 5.1 x 10 -4 to 1.3 x 10 -3 m 2 /kg, respectively. Mean concentration ratios of 137 Cs in Arctic foxes compared to probable prey ranged from 1.0 to 7.9. On Svalbard, transfer of 137 Cs to Arctic foxes is likely to occur via both marine and terrestrial food chains. The relative contribution of marine and terrestrial food sources to the diet of Arctic foxes may vary by location and by season and may lead to either an increase or decrease in the trophic transfer of 137 Cs to Arctic foxes compared to transfer resulting from terrestrial only diets

The evolution of WRKY transcription factors.

Science.gov (United States)

Rinerson, Charles I; Rabara, Roel C; Tripathi, Prateek; Shen, Qingxi J; Rushton, Paul J

2015-02-27

The availability of increasing numbers of sequenced genomes has necessitated a re-evaluation of the evolution of the WRKY transcription factor family. Modern day plants descended from a charophyte green alga that colonized the land between 430 and 470 million years ago. The first charophyte genome sequence from Klebsormidium flaccidum filled a gap in the available genome sequences in the plant kingdom between unicellular green algae that typically have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been previously found in non-plant species but their occurrence has been difficult to explain. Only two WRKY genes are present in the Klebsormidium flaccidum genome and the presence of a Group IIb gene was unexpected because it had previously been thought that Group IIb WRKY genes first appeared in mosses. We found WRKY transcription factor genes outside of the plant lineage in some diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy distribution suggests that lateral gene transfer is responsible. These lateral gene transfer events appear to pre-date the formation of the WRKY groups in flowering plants. Flowering plants contain proteins with domains typical for both resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have evolved numerous times in flowering plants, each type being restricted to specific flowering plant lineages. These chimeric proteins contain not only novel combinations of protein domains but also novel combinations and numbers of WRKY domains. Once formed, R protein WRKY genes may combine different components of signalling pathways that may either create new diversity in signalling or accelerate signalling by short circuiting signalling pathways. We propose that the evolution of WRKY transcription factors includes early lateral gene transfers to non-plant organisms and the occurrence of algal WRKY genes that have no counterparts in flowering plants. We propose two alternative hypotheses

Gray fox (Urocyon cinereoargenteus parasite diversity in central Mexico

Directory of Open Access Journals (Sweden)

Norma Hernández-Camacho

2016-08-01

Full Text Available Mexico has a long history of parasitological studies in communities of vertebrates. However, the mega diversity of the country makes fauna inventories an ongoing priority. Presently, there is little published on the parasite fauna of gray foxes (Urocyon cinereoargenteus Schereber, 1775 and this study provides new records of parasites for gray foxes in central Mexico. It is a continuation of a series of previous parasitological studies conducted with this carnivore in Mexico from 2003 to the present. A total of 24 foxes in the Parque Nacional El Cimatario (PANEC were trapped, anaesthetized, and parasites recovered. The species found were Dirofilaria immitis, Ctenocephalides canis, C. felis, Euhoplopsillus glacialis affinis (first report for gray foxes in Mexico Pulex simulants, and Ixodes sp. Three additional gray fox carcasses were necropsied and the parasites collected were adult nematodes Physaloptera praeputialis and Toxocara canis. The intensive study of the gray fox population selected for the 2013–2015 recent period allowed for a two-fold increase in the number of parasite species recorded for this carnivore since 2003 (nine to 18 parasite species, mainly recording parasitic arthropods, Dirofilaria immitis filariae and adult nematodes. The parasite species recorded are generalists that can survive in anthropic environments; which is characteristic of the present ecological scenario in central Mexico. The close proximity of the PANEC to the city of Santiago de Queretaro suggests possible parasite transmission between the foxes and domestic and feral dogs. Furthermore, packs of feral dogs in the PANEC might have altered habitat use by foxes, with possible impacts on transmission.

The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I

Czech Academy of Sciences Publication Activity Database

Jansa, Petr; Burek, C.; Sander, E. E.; Grummt, I.

2001-01-01

Roč. 29, č. 2 (2001), s. 423-429 ISSN 0305-1048 Institutional research plan: CEZ:AV0Z5052915 Keywords : rDNA transcription * PTRF * transcription reinitiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.373, year: 2001

Adaptive evolution of transcription factor binding sites

Directory of Open Access Journals (Sweden)

Berg Johannes

2004-10-01

Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

OpenAIRE

Hurst, H C; Masson, N; Jones, N C; Lee, K A

1990-01-01

Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We...

Effects of roads on survival of San Clemente Island foxes

Science.gov (United States)

Snow, N.P.; Andelt, William F.; Stanley, T.R.; Resnik, J.R.; Munson, L.

2012-01-01

Roads generate a variety of influences on wildlife populations; however, little is known about the effects of roads on endemic wildlife on islands. Specifically, road-kills of island foxes (Urocyon littoralis) on San Clemente Island (SCI), Channel Islands, California, USA are a concern for resource managers. To determine the effects of roads on island foxes, we radiocollared foxes using a 3-tiered sampling design to represent the entire population in the study area, a sub-population near roads, and a sub-population away from roads on SCI. We examined annual survival rates using nest-survival models, causes of mortalities, and movements for each sample. We found the population had high annual survival (0.90), although survival declined with use of road habitat, particularly for intermediate-aged foxes. Foxes living near roads suffered lower annual survival (0.76), resulting from high frequencies of road-kills (7 of 11 mortalities). Foxes living away from roads had the highest annual survival (0.97). Road-kill was the most prominent cause of mortality detected on SCI, which we estimated as killing 3-8% of the population in the study area annually. Based on movements, we were unable to detect any responses by foxes that minimized their risks from roads. The probabilities of road-kills increased with use of the road habitat, volume of traffic, and decreasing road sinuosity. We recommend that managers should attempt to reduce road-kills by deterring or excluding foxes from entering roads, and attempting to modify behaviors of motorists to be vigilant for foxes. ?? 2011 The Wildlife Society.

Correlates of vulnerability in Chiricahua fox squirrels

Science.gov (United States)

Bret S. Pasch; John L. Koprowski

2005-01-01

Chiricahua fox squirrels (Sciurus nayaritensis chiricahuae) are endemic to the Chiricahua Mountains of southeastern Arizona. A paucity of natural history information and uncertain conservation status served as impetus for us to initiate a descriptive ecological study of the species. We examined reproductive and population ecology of Chiricahua fox...

76 FR 13312 - Drawbridge Operation Regulations; Fox River, Oshkosh, WI

Science.gov (United States)

2011-03-11

...-AA09 Drawbridge Operation Regulations; Fox River, Oshkosh, WI AGENCY: Coast Guard, DHS. ACTION: Notice... National Railway Bridge across the Fox River at Mile 55.72 at Oshkosh, Wisconsin. After careful... On December 8, 2010, we published an NPRM entitled Drawbridge Operation Regulation; Fox River...

Predation on seabirds by red foxes at Shaiak Island, Alaska

Science.gov (United States)

Petersen, M.R.

1982-01-01

Two Red Foxes (Vulpes fulva) that invaded Shaiak Island before the 1976 nesting season had a marked impact on the nesting success of five of seven species of seabirds breeding on the island that year. Common Eiders (Somateria mollissima), Glaucous-winged Gulls (Larus glaucescens), and Common Murres (Uria aalge), that nest in areas accessible to foxes, did not raise any young to fledging. Double-crested Cormorants (Phalacrocorax auritus) were only slightly more successful; 13 (4.3%) of 300 pairs raised one or more young to fledging. Evidence suggested that 21 (35.6%) of 62 pairs of Tufted Puffins (Lunda cirrhata) lost eggs or chicks to foxes, and foxes killed at least 13 (8.3%) of 156 adult puffins on ten sample plots. Conversely, Black-Legged Kittiwakes (Rissa tridactyla) and Pelagic Cormorants (Phalacrocorax pelagicus), which nested primarily on cliffs inaccessible to foxes, lost very few nests. There was no apparent change in general nest site selections by seabirds the following year, when foxes were no longer present. Any avoidance by birds of areas vulnerable to fox predation would probably be discernible only after several years of continuous predation.

Theoretical study on the mechanism of the reaction of FOX-7 with OH and NO2 radicals: bimolecular reactions with low barrier during the decomposition of FOX-7

Science.gov (United States)

Zhang, Ji-Dong; Zhang, Li-Li

2017-12-01

The decomposition of 1,1-diamino-2,2-dinitroethene (FOX-7) attracts great interests, while the studies on bimolecular reactions during the decomposition of FOX-7 are scarce. This study for the first time investigated the bimolecular reactions of OH and NO2 radicals, which are pyrolysis products of ammonium perchlorate (an efficient oxidant usually used in solid propellant), with FOX-7 by computational chemistry methods. The molecular geometries and energies were calculated using the (U)B3LYP/6-31++G(d,p) method. The rate constants of the reactions were calculated by canonical variational transition state theory. We found three mechanisms (H-abstraction, OH addition to C and N atom) for the reaction of OH + FOX-7 and two mechanisms (O abstraction and H abstraction) for the reaction of NO2 + FOX-7. OH radical can abstract H atom or add to C atom of FOX-7 with barriers near to zero, which means OH radical can effectively degrade FOX-7. The O abstraction channel of the reaction of NO2 + FOX-7 results in the formation of NO3 radical, which has never been detected experimentally during the decomposition of FOX-7.

Nutrition and behavior of fennec foxes (Vulpes zerda).

Science.gov (United States)

Dempsey, Janet L; Hanna, Sherilyn J; Asa, Cheryl S; Bauman, Karen L

2009-05-01

Fennec foxes make popular pets because of their small size, minimal odor, and highly social behaviors. They are kept in zoos for conservation and educational programs. The exotic animal practitioner is most likely to be presented with fennec foxes that are overweight because of inappropriate diets or excessive feeding. Clients attempting to hand-rear fennec foxes need advice about formula selection, amounts to feed, protocols for keeping pups warm, and weaning. This article provides information on social behavior, reproduction, and parental behavior, nutrition, and hand-rearing.

IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway.

Science.gov (United States)

Mu, Xiaoyu; Qi, Weihong; Liu, Yunzhang; Zhou, Jianfeng; Li, Yun; Rong, Xiaozhi; Lu, Ling

2017-08-01

Insulin-like growth factor II (IGF-II) can stimulate myogenesis and is critically involved in skeletal muscle differentiation. The presence of negative regulators of this process, however, is not well explored. Here, we showed that in myoblast cells, IGF-II negatively regulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA expression, while constitutive expression of PGC-1α induced myoblast differentiation. These results suggest that the negative regulation of PGC-1α by IGF-II may act as a negative feedback mechanism in IGF-II-induced myogenic differentiation. Reporter assays demonstrated that IGF-II suppresses the basal PGC-1α promoter activity. Blocking the IGF-II signaling pathway increased the endogenous PGC-1α levels. In addition, pharmacological inhibition of PI3 kinase activity prevented the downregulation of PGC-1α but the activation of mTOR was not required for this process. Importantly, further analysis showed that forkhead transcription factor FoxO1 contributes to mediating the effects of IGF-II on PGC-1 promoter activity. These findings indicate that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways.

Alterations in transcription factor binding in radioresistant human melanoma cells after ionizing radiation

International Nuclear Information System (INIS)

Sahijdak, W.M.; Yang, Chin-Rang; Zuckerman, J.S.; Meyers, M.; Boothman, D.A.

1994-01-01

We analyzed alterations in transcription factor binding to specific, known promoter DNA consensus sequences between irradiated and unirradiated radioresistant human melanoma (U1-Mel) cells. The goal of this study was to begin to investigate which transcription factors and DNA-binding sites are responsible for the induction of specific transcripts and proteins after ionizing radiation. Transcription factor binding was observed using DNA band-shift assays and oligonucleotide competition analyses. Confluence-arrested U1-Mel cells were irradiated (4.5 Gy) and harvested at 4 h. Double-stranded oligonucleotides containing known DNA-binding consensus sites for specific transcription factors were used. Increased DNA binding activity after ionizing radiation was noted with oligonucleotides containing the CREB, NF-kB and Sp1 consensus sites. No changes in protein binding to AP-1, AP-2, AP-3, or CTF/NF1, GRE or Oct-1 consensus sequences were noted. X-ray activation of select transcription factors, which bind certain consensus sites in promoters, may cause specific induction or repression of gene transcription. 22 refs., 2 figs

Induction of Epstein-Barr Virus Oncoprotein LMP1 by Transcription Factors AP-2 and Early B Cell Factor

Science.gov (United States)

Noda, Chieko; Narita, Yohei; Watanabe, Takahiro; Yoshida, Masahiro; Ashio, Keiji; Sato, Yoshitaka; Goshima, Fumi; Kanda, Teru; Yoshiyama, Hironori; Tsurumi, Tatsuya; Kimura, Hiroshi

2016-01-01

ABSTRACT Latent membrane protein 1 (LMP1) is a major oncogene essential for primary B cell transformation by Epstein-Barr virus (EBV). Previous studies suggested that some transcription factors, such as PU.1, RBP-Jκ, NF-κB, and STAT, are involved in this expression, but the underlying mechanism is unclear. Here, we identified binding sites for PAX5, AP-2, and EBF in the proximal LMP1 promoter (ED-L1p). We first confirmed the significance of PU.1 and POU domain transcription factor binding for activation of the promoter in latency III. We then focused on the transcription factors AP-2 and early B cell factor (EBF). Interestingly, among the three AP-2-binding sites in the LMP1 promoter, two motifs were also bound by EBF. Overexpression, knockdown, and mutagenesis in the context of the viral genome indicated that AP-2 plays an important role in LMP1 expression in latency II in epithelial cells. In latency III B cells, on the other hand, the B cell-specific transcription factor EBF binds to the ED-L1p and activates LMP1 transcription from the promoter. IMPORTANCE Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is crucial for B cell transformation and oncogenesis of other EBV-related malignancies, such as nasopharyngeal carcinoma and T/NK lymphoma. Its expression is largely dependent on the cell type or condition, and some transcription factors have been implicated in its regulation. However, these previous reports evaluated the significance of specific factors mostly by reporter assay. In this study, we prepared point-mutated EBV at the binding sites of such transcription factors and confirmed the importance of AP-2, EBF, PU.1, and POU domain factors. Our results will provide insight into the transcriptional regulation of the major oncogene LMP1. PMID:26819314

Echinococcus multilocularis found in 2 foxes in Southern Jutland

DEFF Research Database (Denmark)

Enemark, Heidi L.

2013-01-01

The news about these findings were released this morning [10 Jul 2013]. However, later today we detected another positive fox, from the same area, which is not mentioned in the press release (The press release, in Danish, can be found at http://www.vet.dtu.dk/Nyheder/Nyhed?id=%7bDC4E4263- 505A-4554......-BD23-BB1C85C34327%7d). Since September 2011 we have surveyed _E. multilocularis_ in wild carnivores. A total of 856 carnivores have been studied so far: 692 foxes, 150 raccoon dogs, 11 badgers, 3 raccoons, and one wolf. Of these, 7 foxes were positive, all of them originating from the same area...... in southern Denmark -- the Hojer region near the German border. At present, 32 foxes have been analyzed from this area (local prevalence: 7/32 = 21.9 percent; national prevalence: 7/692 = 1.0 percent). The 3 new findings were from foxes shot between December 2012 and February 2013 and revealed worm burdens...

Genetic signatures of adaptation revealed from transcriptome sequencing of Arctic and red foxes

OpenAIRE

Kumar, Vikas; Kutschera, Verena E.; Nilsson, Maria A.; Janke, Axel

2015-01-01

Background The genus Vulpes (true foxes) comprises numerous species that inhabit a wide range of habitats and climatic conditions, including one species, the Arctic fox (Vulpes lagopus) which is adapted to the arctic region. A close relative to the Arctic fox, the red fox (Vulpes vulpes), occurs in subarctic to subtropical habitats. To study the genetic basis of their adaptations to different environments, transcriptome sequences from two Arctic foxes and one red fox individual were generated...

Transcription profile of Escherichia coli: genomic SELEX search for regulatory targets of transcription factors.

Science.gov (United States)

Ishihama, Akira; Shimada, Tomohiro; Yamazaki, Yukiko

2016-03-18

Bacterial genomes are transcribed by DNA-dependent RNA polymerase (RNAP), which achieves gene selectivity through interaction with sigma factors that recognize promoters, and transcription factors (TFs) that control the activity and specificity of RNAP holoenzyme. To understand the molecular mechanisms of transcriptional regulation, the identification of regulatory targets is needed for all these factors. We then performed genomic SELEX screenings of targets under the control of each sigma factor and each TF. Here we describe the assembly of 156 SELEX patterns of a total of 116 TFs performed in the presence and absence of effector ligands. The results reveal several novel concepts: (i) each TF regulates more targets than hitherto recognized; (ii) each promoter is regulated by more TFs than hitherto recognized; and (iii) the binding sites of some TFs are located within operons and even inside open reading frames. The binding sites of a set of global regulators, including cAMP receptor protein, LeuO and Lrp, overlap with those of the silencer H-NS, suggesting that certain global regulators play an anti-silencing role. To facilitate sharing of these accumulated SELEX datasets with the research community, we compiled a database, 'Transcription Profile of Escherichia coli' (www.shigen.nig.ac.jp/ecoli/tec/). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

FOXE1 Association with both Isolated Cleft Lip with or without Cleft Palate; and Isolated Cleft Palate

DEFF Research Database (Denmark)

Moreno, Lina M; Mansilla, Maria Adela; Bullard, Steve A

2009-01-01

Nonsyndromic orofacial clefts are a common complex birth defect caused by genetic and environmental factors and/or their interactions. A previous genome-wide linkage scan discovered a novel locus for cleft lip with or without cleft palate (CL/P) at 9q22-q33. To identify the etiologic gene, we......) and rs4460498 (p=6.51E-12) were located inside a 70Kb high LD block containing FOXE1. Association signals for Caucasians and Asians clustered 5' and 3' of FOXE1, respectively. Isolated cleft palate (CP) was also associated indicating that FOXE1 plays a role in two phenotypes thought to be genetically...

Identification of transcription-factor genes expressed in the Arabidopsis female gametophyte

Directory of Open Access Journals (Sweden)

Kang Il-Ho

2010-06-01

Full Text Available Abstract Background In flowering plants, the female gametophyte is typically a seven-celled structure with four cell types: the egg cell, the central cell, the synergid cells, and the antipodal cells. These cells perform essential functions required for double fertilization and early seed development. Differentiation of these distinct cell types likely involves coordinated changes in gene expression regulated by transcription factors. Therefore, understanding female gametophyte cell differentiation and function will require dissection of the gene regulatory networks operating in each of the cell types. These efforts have been hampered because few transcription factor genes expressed in the female gametophyte have been identified. To identify such genes, we undertook a large-scale differential expression screen followed by promoter-fusion analysis to detect transcription-factor genes transcribed in the Arabidopsis female gametophyte. Results Using quantitative reverse-transcriptase PCR, we analyzed 1,482 Arabidopsis transcription-factor genes and identified 26 genes exhibiting reduced mRNA levels in determinate infertile 1 mutant ovaries, which lack female gametophytes, relative to ovaries containing female gametophytes. Spatial patterns of gene transcription within the mature female gametophyte were identified for 17 transcription-factor genes using promoter-fusion analysis. Of these, ten genes were predominantly expressed in a single cell type of the female gametophyte including the egg cell, central cell and the antipodal cells whereas the remaining seven genes were expressed in two or more cell types. After fertilization, 12 genes were transcriptionally active in the developing embryo and/or endosperm. Conclusions We have shown that our quantitative reverse-transcriptase PCR differential-expression screen is sufficiently sensitive to detect transcription-factor genes transcribed in the female gametophyte. Most of the genes identified in this

Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

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Katie L Lannan

2015-02-01

Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

O-GlcNAc inhibits interaction between Sp1 and Elf-1 transcription factors

International Nuclear Information System (INIS)

Lim, Kihong; Chang, Hyo-Ihl

2009-01-01

The novel protein modification, O-linked N-acetylglucosamine (O-GlcNAc), plays an important role in various aspects of cell regulation. Although most of nuclear transcription regulatory factors are modified by O-GlcNAc, O-GlcNAc effects on transcription remain largely undefined yet. In this study, we show that O-GlcNAc inhibits a physical interaction between Sp1 and Elf-1 transcription factors, and negatively regulates transcription of placenta and embryonic expression oncofetal protein gene (Pem). These findings suggest that O-GlcNAc inhibits Sp1-mediated gene transcription possibly by interrupting Sp1 interaction with its cooperative factor.

Single crystal spectrometer FOX at KENS

International Nuclear Information System (INIS)

Takahashi, M.

2001-01-01

Single crystal spectrometer FOX installed at H1 thermal neutron line on KENS has been renewed recently for the measurement of very weak scattering. We have installed a multidetector system of 36 linearly placed 3 He detectors with collimators instead of former four-circle diffractometer and scintillator detectors. Though the system is quite simple, a large two-dimensional reciprocal space is observed effectively with high S/N rate on new FOX. (author)

Eukaryotic transcription factors

DEFF Research Database (Denmark)

Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

2017-01-01

Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... regions with function-related, short sequence motifs and molecular recognition features with structural propensities. This review focuses on molecular aspects of TFs, which represent paradigms of ID-related features. Through specific examples, we review how the ID-associated flexibility of TFs enables....... It is furthermore emphasized how classic biochemical concepts like allostery, conformational selection, induced fit, and feedback regulation are undergoing a revival with the appreciation of ID. The review also describes the most recent advances based on computational simulations of ID-based interaction mechanisms...

The transcription fidelity factor GreA impedes DNA break repair.

Science.gov (United States)

Sivaramakrishnan, Priya; Sepúlveda, Leonardo A; Halliday, Jennifer A; Liu, Jingjing; Núñez, María Angélica Bravo; Golding, Ido; Rosenberg, Susan M; Herman, Christophe

2017-10-12

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

Specificity versus redundancy in the RAP2.4 transcription factor family of Arabidopsis thaliana: transcriptional regulation of genes for chloroplast peroxidases.

Science.gov (United States)

Rudnik, Radoslaw; Bulcha, Jote Tafese; Reifschneider, Elena; Ellersiek, Ulrike; Baier, Margarete

2017-08-23

The Arabidopsis ERFIb / RAP2.4 transcription factor family consists of eight members with highly conserved DNA binding domains. Selected members have been characterized individually, but a systematic comparison is pending. The redox-sensitive transcription factor RAP2.4a mediates chloroplast-to-nucleus redox signaling and controls induction of the three most prominent chloroplast peroxidases, namely 2-Cys peroxiredoxin A (2CPA) and thylakoid- and stromal ascorbate peroxidase (tAPx and sAPx). To test the specificity and redundancy of RAP2.4 transcription factors in the regulation of genes for chloroplast peroxidases, we compared the DNA-binding sites of the transcription factors in tertiary structure models, analyzed transcription factor and target gene regulation by qRT-PCR in RAP2.4, 2-Cys peroxiredoxin and ascorbate peroxidase T-DNA insertion lines and RAP2.4 overexpressing lines of Arabidopsis thaliana and performed promoter binding studies. All RAP2.4 proteins bound the tAPx promoter, but only the four RAP2.4 proteins with identical DNA contact sites, namely RAP2.4a, RAP2.4b, RAP2.4d and RAP2.4h, interacted stably with the redox-sensitive part of the 2CPA promoter. Gene expression analysis in RAP2.4 knockout lines revealed that RAP2.4a is the only one supporting 2CPA and chloroplast APx expression. Rap2.4h binds to the same promoter region as Rap2.4a and antagonizes 2CPA expression. Like the other six RAP2.4 proteins, Rap2.4 h promotes APx mRNA accumulation. Chloroplast ROS signals induced RAP2.4b and RAP2.4d expression, but these two transcription factor genes are (in contrast to RAP2.4a) insensitive to low 2CP availability, and their expression decreased in APx knockout lines. RAP2.4e and RAP2.4f gradually responded to chloroplast APx availability and activated specifically APx expression. These transcription factors bound, like RAP2.4c and RAP2.4g, the tAPx promoter, but hardly the 2CPA promoter. The RAP2.4 transcription factors form an environmentally and

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

Science.gov (United States)

Perdigão, Pedro; Gaj, Thomas; Santa-Marta, Mariana; Barbas, Carlos F; Goncalves, Joao

2016-01-01

The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors.

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Pedro Perdigão

Full Text Available The presence of replication-competent HIV-1 -which resides mainly in resting CD4+ T cells--is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.

Landscape genetics of the nonnative red fox of California.

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Sacks, Benjamin N; Brazeal, Jennifer L; Lewis, Jeffrey C

2016-07-01

Invasive mammalian carnivores contribute disproportionately to declines in global biodiversity. In California, nonnative red foxes (Vulpes vulpes) have significantly impacted endangered ground-nesting birds and native canids. These foxes derive primarily from captive-reared animals associated with the fur-farming industry. Over the past five decades, the cumulative area occupied by nonnative red fox increased to cover much of central and southern California. We used a landscape-genetic approach involving mitochondrial DNA (mtDNA) sequences and 13 microsatellites of 402 nonnative red foxes removed in predator control programs to investigate source populations, contemporary connectivity, and metapopulation dynamics. Both markers indicated high population structuring consistent with origins from multiple introductions and low subsequent gene flow. Landscape-genetic modeling indicated that population connectivity was especially low among coastal sampling sites surrounded by mountainous wildlands but somewhat higher through topographically flat, urban and agricultural landscapes. The genetic composition of populations tended to be stable for multiple generations, indicating a degree of demographic resilience to predator removal programs. However, in two sites where intensive predator control reduced fox abundance, we observed increases in immigration, suggesting potential for recolonization to counter eradication attempts. These findings, along with continued genetic monitoring, can help guide localized management of foxes by identifying points of introductions and routes of spread and evaluating the relative importance of reproduction and immigration in maintaining populations. More generally, the study illustrates the utility of a landscape-genetic approach for understanding invasion dynamics and metapopulation structure of one of the world's most destructive invasive mammals, the red fox.

Autochthonous Hepatozoon infection in hunting dogs and foxes from the Czech Republic

Czech Academy of Sciences Publication Activity Database

Mitková, B.; Hrazdilová, K.; Steinbauer, V.; D'Amico, G.; Mihalca, A. D.; Modrý, David

2016-01-01

Roč. 115, č. 11 (2016), s. 4167-4171 ISSN 0932-0113 Institutional support: RVO:60077344 Keywords : Hepatozoon canis * dogs * red fox es * Czech Republic * autochthonous infection Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.329, year: 2016

Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

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Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

2015-10-01

Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV

Distemper in raccoons and foxes suspected of having rabies

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Habermann, R.T.; Herman, C.M.; Williams, F.P.

1958-01-01

1) Twenty-one raccoons and 3 red foxes were collected from areas where suspected rabies occurred. All were found to be nonrabid. 2) Distemper was diagnosed in 14 of the 21 raccoons by demonstrating intracytoplasmic and intranuclear inclusions in the brain and visceral tissues. Two of the 3 foxes were considered to have distemper; the clinical signs were typical and mouse inoculation tests were negative for rabies. 3) Deaths of the other 7 raccoons were attributed to: leishmaniasis 1, gastritis 1, bronchopneumonia 1, parasitism 2, car injury 1; 1 showed no significant lesions. The death of 1 fox was attributed to parasitism. 4) Distemper may be a frequent cause of death in raccoons and foxes, in epizootics which simulate rabies.

Eucoleus boehmi infection in red fox (Vulpes vulpes) from Italy.

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Veronesi, Fabrizia; Morganti, Giulia; di Cesare, Angela; Lepri, Elvio; Cassini, Rudi; Zanet, Stefania; Deni, Dario; Chiari, Mario; Ferroglio, Ezio

2014-12-15

In the last decade an increase of the number of red foxes in anthropized habitats across European countries, including Italy, has been observed. This pones implications in terms of disease transmission between wildlife and domestic animals; in fact, there are evidences of the role of foxes as reservoirs and amplifiers of a broad spectrum of parasites infecting pets. The present study evaluated the prevalence of Eucoleus boehmi, an emerging extra-intestinal nematodes of the Capillariinae subfamily, in red foxes. The nasal passages and sinuses of 179 red foxes culled from several areas of northern and central Italy were inspected and the mucosal surfaces were scrapped and examined for adult nematodes and eggs, microscopically and genetically identified. Overall 55 foxes (30.7%) were found to be infected with E. boehmi, i.e. 27 on inspection of the nasal passages and sinuses and 28 on mucosal flush and scraping. The occurrence of E. boehmi was significantly (p fox body condition (mean: 7.8 specimens). These results show that E. boehmi is highly prevalent in the red fox populations of certain areas of Italy. Epidemiological implications are discussed, with a special focus on the role that this wild canid may have in the increasing transmission of nasal eucoleosis to domestic dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.

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Alexandra Dumitriu

2012-06-01

Full Text Available Parkinson disease (PD is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9 of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1 transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes, suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs selected from a recent meta-analysis of PD genome-wide association studies (GWAS were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK gene and a probe in the spermine oxidase (SMOX gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

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Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

2018-05-18

A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer

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Makito Mizunuma

2016-05-01

Full Text Available Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX, and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ERα, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3. The effects of estrogen on ERα, FOXP1, KRAS, and PTEN expression were analyzed in telomerase-immortalized human endometrial stromal cells (T HESCs by Western blotting. Western blotting was also used to examine the effect of FOXP1 plasmid DNA or siRNA transfection on KRAS and PTEN expression in Ishikawa cells (well differentiated endometrioid adenocarcinoma, HEC-50B cells (poorly differentiated endometrioid adenocarcinoma, and T HESCs, respectively. FOXP1 was expressed in normal and malignant endometrium, but the rate of expression was different depending upon menstrual cycle and pathological grade of malignancy. FOXP1 expression in nucleus and cytoplasm of grade 3 endometrioid cancers was significantly lower than that of grade 1 and 2 ones. Estradiol increased levels of FOXP1 and KRAS expression in a dose- and time-dependent manner in T HESCs cells, and FOXP1 transfection or knockdown led to increase or decrease of KRAS expression but not PTEN. KRAS expression level was significantly related to FOXP1 and ERα levels in cancer tissues. Estradiol did not affect KRAS expression in T HESCs cells transfected with FOXP1 siRNA. These results suggest that FOXP1 is involved in estrogen dependent endometrial cancers through KRAS pathway.

Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

DEFF Research Database (Denmark)

Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

2006-01-01

Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

Screening for infection of Trichinella in red fox (Vulpes vulpes) in Denmark

DEFF Research Database (Denmark)

Enemark, Heidi L.; Bjørn, H.; Henriksen, S.A.

2000-01-01

A total of 6141 foxes (Vulpes vulpes) were examined for infection with Trichinella. The foxes were killed in Denmark during the hunting season 1995-1996 and 1997-1998; 3133 and 3008, respectively, Foxes included in the investigation came from throughout the country with the exception of the island...... of Bornholm. The right foreleg from each fox was submitted for investigation. The legs were stored at -20 degrees C for 3-10 months prior to examination. Following thawing, muscle tissue (10 g) from each leg was examined by trichinoscopy and by a pepsin-HCl digestion technique. In 1995-1996, three foxes were...... found positive corresponding to a prevalence of 0.001. Each of the infected foxes harboured an extremely low infection, i.e, about one larva per 10 g muscle tissue. It was not possible to obtain sufficient larval material for species identification, All three foxes were shot in the vicinity of a small...

Tracing the fox family tree: the North American red fox has a diverse ancestry forged during successive ice ages

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Gail Wells; Keith Aubry

2011-01-01

The red fox is one of the most widespread and adaptable mammals on Earth. In the American West, however, there are populations of native red foxes that occur only in alpine and subalpine habitats, which may be at risk from human-caused and natural pressures. One potential threat is global climate change, which is likely to reduce both the amount and connectivity of...

Determination of specificity influencing residues for key transcription factor families

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Patel, Ronak Y.; Garde, Christian; Stormo, Gary D.

2015-01-01

Transcription factors (TFs) are major modulators of transcription and subsequent cellular processes. The binding of TFs to specific regulatory elements is governed by their specificity. Considering the gap between known TFs sequence and specificity, specificity prediction frameworks are highly de...

Mitochondrial genomes suggest rapid evolution of dwarf California Channel Islands foxes (Urocyon littoralis).

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Hofman, Courtney A; Rick, Torben C; Hawkins, Melissa T R; Funk, W Chris; Ralls, Katherine; Boser, Christina L; Collins, Paul W; Coonan, Tim; King, Julie L; Morrison, Scott A; Newsome, Seth D; Sillett, T Scott; Fleischer, Robert C; Maldonado, Jesus E

2015-01-01

Island endemics are typically differentiated from their mainland progenitors in behavior, morphology, and genetics, often resulting from long-term evolutionary change. To examine mechanisms for the origins of island endemism, we present a phylogeographic analysis of whole mitochondrial genomes from the endangered island fox (Urocyon littoralis), endemic to California's Channel Islands, and mainland gray foxes (U. cinereoargenteus). Previous genetic studies suggested that foxes first appeared on the islands >16,000 years ago, before human arrival (~13,000 cal BP), while archaeological and paleontological data supported a colonization >7000 cal BP. Our results are consistent with initial fox colonization of the northern islands probably by rafting or human introduction ~9200-7100 years ago, followed quickly by human translocation of foxes from the northern to southern Channel Islands. Mitogenomes indicate that island foxes are monophyletic and most closely related to gray foxes from northern California that likely experienced a Holocene climate-induced range shift. Our data document rapid morphological evolution of island foxes (in ~2000 years or less). Despite evidence for bottlenecks, island foxes have generated and maintained multiple mitochondrial haplotypes. This study highlights the intertwined evolutionary history of island foxes and humans, and illustrates a new approach for investigating the evolutionary histories of other island endemics.

Hoxa5 overexpression correlates with IGFBP1 upregulation and postnatal dwarfism: evidence for an interaction between Hoxa5 and Forkhead box transcription factors.

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Foucher, Isabelle; Volovitch, Michel; Frain, Monique; Kim, J Julie; Souberbielle, Jean-Claude; Gan, Lixia; Unterman, Terry G; Prochiantz, Alain; Trembleau, Alain

2002-09-01

Transgenic mice expressing the homeobox gene Hoxa5 under the control of Hoxb2 regulatory elements present a growth arrest during weeks two and three of postnatal development, resulting in proportionate dwarfism. These mice present a liver phenotype illustrated by a 12-fold increase in liver insulin-like growth factor binding protein 1 (IGFBP1) mRNA and a 50% decrease in liver insulin-like growth factor 1 (IGF1) mRNA correlated with a 50% decrease in circulating IGF1. We show that the Hoxa5 transgene is expressed in the liver of these mice, leading to an overexpression of total (endogenous plus transgene) Hoxa5 mRNA in this tissue. We have used several cell lines to investigate a possible physiological interaction of Hoxa5 with the main regulator of IGFBP1 promoter activity, the Forkhead box transcription factor FKHR. In HepG2 cells, Hoxa5 has little effect by itself but inhibits the FKHR-dependent activation of the IGFBP1 promoter. In HuF cells, Hoxa5 cooperates with FKHR to dramatically enhance IGFBP1 promoter activity. This context-dependent physiological interaction probably corresponds to the existence of a direct interaction between Hoxa5 and FKHR and FoxA2/HNF3beta, as demonstrated by pull-down experiments achieved either in vitro or after cellular co-expression. In conclusion, we propose that the impaired growth observed in this transgenic line relates to a liver phenotype best explained by a direct interaction between Hoxa5 and liver-specific Forkhead box transcription factors, in particular FKHR but also Foxa2/HNF3beta. Because Hoxa5 and homeogenes of the same paralog group are normally expressed in the liver, the present results raise the possibility that homeoproteins, in addition to their established role during early development, regulate systemic physiological functions.

Angiostrongylus vasorum infection in foxes (Vulpes vulpes) in Cornwall.

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Simpson, V R

1996-11-02

A post mortem examination on a young fox which had been observed to be clinically ill revealed a severe infection with Angiostrongylus vasorum. A further 11 foxes were examined and four were infected with the parasite; three of these also had advanced lesions of sarcoptic mange. The cases all occurred outside the previously defined focus of endemic infection for dogs in Cornwall and they appear to be the first recorded cases of A vasorum in foxes in the United Kingdom.

Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

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Katy Milne

Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

A transcript cleavage factor of Mycobacterium tuberculosis important for its survival.

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Arnab China

Full Text Available After initiation of transcription, a number of proteins participate during elongation and termination modifying the properties of the RNA polymerase (RNAP. Gre factors are one such group conserved across bacteria. They regulate transcription by projecting their N-terminal coiled-coil domain into the active center of RNAP through the secondary channel and stimulating hydrolysis of the newly synthesized RNA in backtracked elongation complexes. Rv1080c is a putative gre factor (MtbGre in the genome of Mycobacterium tuberculosis. The protein enhanced the efficiency of promoter clearance by lowering abortive transcription and also rescued arrested and paused elongation complexes on the GC rich mycobacterial template. Although MtbGre is similar in domain organization and shares key residues for catalysis and RNAP interaction with the Gre factors of Escherichia coli, it could not complement an E. coli gre deficient strain. Moreover, MtbGre failed to rescue E. coli RNAP stalled elongation complexes, indicating the importance of specific protein-protein interactions for transcript cleavage. Decrease in the level of MtbGre reduced the bacterial survival by several fold indicating its essential role in mycobacteria. Another Gre homolog, Rv3788 was not functional in transcript cleavage activity indicating that a single Gre is sufficient for efficient transcription of the M. tuberculosis genome.

Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam.

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Nukaga, Michiyoshi; Papp-Wallace, Krisztina M; Hoshino, Tyuji; Lefurgy, Scott T; Bethel, Christopher R; Barnes, Melissa D; Zeiser, Elise T; Johnson, J Kristie; Bonomo, Robert A

2018-05-01

Ceftazidime-avibactam is a "second-generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases, and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases, is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in the Citrobacter AmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active-site topologies affect avibactam inhibition, we tested a panel of clinical Enterobacteriaceae isolates producing bla FOX using ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producing bla FOX ; two isolates, one expressing bla FOX-4 and the other producing bla FOX-5 , displayed an MIC of 16 μg/ml for the combination. FOX-4 possessed a k 2 / K value of 1,800 ± 100 M -1 · s -1 and an off rate ( k off ) of 0.0013 ± 0.0003 s -1 Mass spectrometry showed that the FOX-4-avibactam complex did not undergo chemical modification for 24 h. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5-Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the Pseudomonas -derived cephalosporinase 1 (PDC-1)-avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen

Lattice Three-Species Models of the Spatial Spread of Rabies among FOXES

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Benyoussef, A.; Boccara, N.; Chakib, H.; Ez-Zahraouy, H.

Lattice models describing the spatial spread of rabies among foxes are studied. In these models, the fox population is divided into three-species: susceptible (S), infected or incubating (I), and infectious or rabid (R). They are based on the fact that susceptible and incubating foxes are territorial while rabid foxes have lost their sense of direction and move erratically. Two different models are investigated: a one-dimensional coupled-map lattice model, and a two-dimensional automata network model. Both models take into account the short-range character of the infection process and the diffusive motion of rabid foxes. Numerical simulations show how the spatial distribution of rabies, and the speed of propagation of the epizootic front depend upon the carrying capacity of the environment and diffusion of rabid foxes out of their territory.

Inhibition of factor-dependent transcription termination in ...

Indian Academy of Sciences (India)

Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating. H-NS-DNA interactions in vivo. DEEPTI CHANDRAPRAKASH and ASWIN SAI NARAIN SESHASAYEE. Chromatin immunoprecipitation. MG1655 hns::3xFLAG cells were grown in liquid LB me-.

Endoparasites of the raccoon dog (Nyctereutes procyonoides) and the red fox (Vulpes vulpes) in Denmark 2009-2012 - A comparative study.

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Al-Sabi, Mohammad Nafi Solaiman; Chriél, Mariann; Jensen, Trine Hammer; Enemark, Heidi Larsen

2013-12-01

Invasive species negatively influence the biodiversity of the ecosystems they invade and may introduce pathogens to native species. Raccoon dogs have very successfully invaded Europe, including, recently, Denmark. This study included analyses of gastrointestinal helminths and Trichinella spp. from 99 raccoon dogs and 384 native red foxes collected from October 2009 to March 2012. The sedimentation and counting method used revealed that raccoon dogs and foxes harboured 9 and 13 different helminth species, respectively, of which several known to be zoonotic. Significantly more nematode and cestode species were found in foxes while raccoon dogs had more trematode species. Rodent transmitted parasites were more prevalent in foxes, while amphibian transmitted parasites were more prevalent in raccoon dogs. One fox was infected with Echinococcus multilocularis (0.3%), while no Trichinella spp. were detected in raccoon dogs or foxes. The trematode Brachylaima tokudai was detected for the first time in Denmark in five of 384 foxes (1.3%). Prevalences of Pygidiopsis summa (3.0% and 3.4%) and Cryptocotyle spp. (15.2% and 15.4%) were comparable in raccoon dogs and foxes, respectively. Four helminth species were more prevalent in foxes than in raccoon dogs: Toxocara canis (60.9% and 13.1%); Uncinaria stenocephala (84.1% and 48.5%); Mesocestoides spp. (42.7% and 23.2%); and Taenia spp. (30.7% and 2.0%), respectively. Three helminth species were more prevalent in raccoon dogs than in foxes: Dipylidium caninum (5.1% and 0.3%); Mesorchis denticulatus (38.4% and 4.2%); and Alaria alata (69.7% and 34.4%), respectively. T. canis was more abundant in foxes while A. alata was more abundant in raccoon dogs. The intestinal distribution of a number of helminth species was comparable between hosts, but highly variable between parasite species. Inherent biological factors and host invasion of new areas might have shaped these marked differences in helminth fauna between the invasive raccoon

Effects of military-authorized activities on the San Joaquin kit fox (Vulpes velox macrotis) at Camp Roberts Army National Guard Training Site, California

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Berry, W.H.; Standley, W.G.; O`Farrell, T.P.; Kato, T.T.

1992-10-01

The effects of military-authorized activities on San Joaquin kit fox (Vulpes velox macrotis) were investigated at Camp Roberts Army National Guard Training Site from 1988 to 1991. Military-authorized activities included military training exercises, facilities maintenance, new construction, controlled burning, livestock grazing, and public-access hunting. Positive effects of the military included habitat preservation, preactivity surveys, and natural resources management practices designed to conserve kit foxes and their habitat. Perceived negative effects such as entrapment in dens, shootings during military exercises, and accidental poisoning were not observed. Foxes were observed in areas being used simultaneously by military units. Authorized activities were known to have caused the deaths of three of 52 radiocollared foxes recovered dead: one became entangled in concertina wire, one was believed shot by a hunter, and one was struck by a vehicle. Entanglement in communication wire may have contributed to the death of another radiocollared fox that was killed by a predator. Approximately 10% of kit fox dens encountered showed evidence of vehicle traffic, but denning sites did not appear to be a limiting factor for kit foxes.

Expression of fox-related genes in the skin follicles of Inner Mongolia cashmere goat.

Science.gov (United States)

Han, Wenjing; Li, Xiaoyan; Wang, Lele; Wang, Honghao; Yang, Kun; Wang, Zhixin; Wang, Ruijun; Su, Rui; Liu, Zhihong; Zhao, Yanhong; Zhang, Yanjun; Li, Jinquan

2018-03-01

This study investigated the expression of genes in cashmere goats at different periods of their fetal development. Bioinformatics analysis was used to evaluate data obtained by transcriptome sequencing of fetus skin samples collected from Inner Mongolia cashmere goats on days 45, 55, and 65 of fetal age. We found that FoxN1 , FoxE1 , and FoxI3 genes of the Fox gene family were probably involved in the growth and development of the follicle and the formation of hair, which is consistent with previous findings. Real-time quantitative polymerase chain reaction detecting system and Western blot analysis were employed to study the relative differentially expressed genes FoxN1 , FoxE1 , and FoxI3 in the body skin of cashmere goat fetuses and adult individuals. This study provided new fundamental information for further investigation of the genes related to follicle development and exploration of their roles in hair follicle initiation, growth, and development.

Expression of fox-related genes in the skin follicles of Inner Mongolia cashmere goat

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Wenjing Han

2018-03-01

Full Text Available Objective This study investigated the expression of genes in cashmere goats at different periods of their fetal development. Methods Bioinformatics analysis was used to evaluate data obtained by transcriptome sequencing of fetus skin samples collected from Inner Mongolia cashmere goats on days 45, 55, and 65 of fetal age. Results We found that FoxN1, FoxE1, and FoxI3 genes of the Fox gene family were probably involved in the growth and development of the follicle and the formation of hair, which is consistent with previous findings. Real-time quantitative polymerase chain reaction detecting system and Western blot analysis were employed to study the relative differentially expressed genes FoxN1, FoxE1, and FoxI3 in the body skin of cashmere goat fetuses and adult individuals. Conclusion This study provided new fundamental information for further investigation of the genes related to follicle development and exploration of their roles in hair follicle initiation, growth, and development.

"Reversed" intraguild predation: red fox cubs killed by pine marten.

Science.gov (United States)

Brzeziński, Marcin; Rodak, Lukasz; Zalewski, Andrzej

2014-01-01

Camera traps deployed at a badger Meles meles set in mixed pine forest in north-eastern Poland recorded interspecific killing of red fox Vulpes vulpes cubs by pine marten Martes martes . The vixen and her cubs settled in the set at the beginning of May 2013, and it was abandoned by the badgers shortly afterwards. Five fox cubs were recorded playing in front of the den each night. Ten days after the first recording of the foxes, a pine marten was filmed at the set; it arrived in the morning, made a reconnaissance and returned at night when the vixen was away from the set. The pine marten entered the den several times and killed at least two fox cubs. It was active at the set for about 2 h. This observation proves that red foxes are not completely safe from predation by smaller carnivores, even those considered to be subordinate species in interspecific competition.

A rural mail-carrier index of North Dakota red foxes

Science.gov (United States)

Allen, S.H.; Sargeant, A.B.

1975-01-01

Rural mail-carrier sightings of red foxes (Vulpes vulpes) during mid-April, -July, and -September of 1969-73 were compared to spring fox family estimates derived by aerial searches of six townships. The mid-April mail-carrier index reflected annual fox density changes on the six townships (correlation coefficient = 0.958) . Random exclusions of individual mail-carrier reports indicated participation could decline 40 percent without affecting index accuracy.

Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

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Qi Yuan(Alan

2010-01-01

Full Text Available Abstract The problem of uncovering transcriptional regulation by transcription factors (TFs based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ( status and Estrogen Receptor negative ( status, respectively.

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

Energy Technology Data Exchange (ETDEWEB)

Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

2014-04-04

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

International Nuclear Information System (INIS)

Chu, Tian-Li; Zhao, Hong-Meng; Li, Yue; Chen, Ao-Xiang; Sun, Xuan; Ge, Jie

2014-01-01

Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy

Myocardin-related transcription factors are required for cardiac development and function

OpenAIRE

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2015-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

Trichinella britovi in a red fox (Vulpes vulpes) from Portugal.

Science.gov (United States)

Lopes, Ana Patrícia; Vila-Viçosa, Maria João; Coutinho, Teresa; Cardoso, Luís; Gottstein, Bruno; Müller, Norbert; Cortes, Helder C E

2015-06-15

Trichinellosis is one of the most important foodborne parasitic zoonoses, caused by nematodes of the genus Trichinella. Pigs and other domestic and wild animals, including red foxes (Vulpes vulpes), are sources of Trichinella infection for human beings. Trichinella britovi is the major agent of infection in sylvatic animals and the most important species circulating in the European wildlife. The present study aimed at assessing Trichinella spp. infection in red foxes from the North of Portugal. Forty-seven carcasses of wild red foxes shot during the official hunting season or killed in road accidents were obtained between November 2008 and March 2010. In order to identify the presence of Trichinella spp. larvae in red foxes, an individual artificial digestion was performed using approximately 30 g of muscle samples. Larvae of Trichinella spp. were detected in one (2.1%) out of the 47 assessed foxes. After a multiplex polymerase chain reaction analysis, T. britovi was molecularly identified as the infecting species. The recognition of T. britovi in a red fox confirms that a sylvatic cycle is present in the North of Portugal and that the local prevalence of Trichinella infection in wildlife must not be ignored due to its underlying zoonotic risks. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors

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Kamesh Narasimhan

2014-01-01

Conclusion: Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies, to address the substantial challenges involved in achieving target selectivity.

Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

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Mi-Young Kim

2012-01-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.

Interactome analysis of transcriptional coactivator multiprotein bridging factor 1 unveils a yeast AP-1-like transcription factor involved in oxidation tolerance of mycopathogen Beauveria bassiana.

Science.gov (United States)

Chu, Xin-Ling; Dong, Wei-Xia; Ding, Jin-Li; Feng, Ming-Guang; Ying, Sheng-Hua

2018-02-01

Oxidation tolerance is an important determinant to predict the virulence and biocontrol potential of Beauveria bassiana, a well-known entomopathogenic fungus. As a transcriptional coactivator, multiprotein bridging factor 1 mediates the activity of transcription factor in diverse physiological processes, and its homolog in B. bassiana (BbMBF1) contributes to fungal oxidation tolerance. In this study, the BbMBF1-interactomes under oxidative stress and normal growth condition were deciphered by mass spectrometry integrated with the immunoprecipitation. BbMBF1p factor has a broad interaction with proteins that are involved in various cellular processes, and this interaction is dynamically regulated by oxidative stress. Importantly, a B. bassiana homolog of yeast AP-1-like transcription factor (BbAP-1) was specifically associated with the BbMBF1-interactome under oxidation and significantly contributed to fungal oxidation tolerance. In addition, qPCR analysis revealed that several antioxidant genes are jointly controlled by BbAP-1 and BbMBF1. Conclusively, it is proposed that BbMBF1p protein mediates BbAP-1p factor to transcribe the downstream antioxidant genes in B. bassiana under oxidative stress. This study demonstrates for the first time a proteomic view of the MBF1-interactome in fungi, and presents an initial framework to probe the transcriptional mechanism involved in fungal response to oxidation, which will provide a new strategy to improve the biocontrol efficacy of B. bassiana.

Emerging roles and regulation of MiT/TFE transcriptional factors.

Science.gov (United States)

Yang, Min; Liu, En; Tang, Li; Lei, Yuanyuan; Sun, Xuemei; Hu, Jiaxi; Dong, Hui; Yang, Shi-Ming; Gao, Mingfa; Tang, Bo

2018-06-15

The MiT/TFE transcription factors play a pivotal role in the regulation of autophagy and lysosomal biogenesis. The subcellular localization and activity of MiT/TFE proteins are primarily regulated through phosphorylation. And the phosphorylated protein is retained in the cytoplasm and subsequently translocates to the nucleus upon dephosphorylation, where it stimulates the expression of hundreds of genes, leading to lysosomal biogenesis and autophagy induction. The transcription factor-mediated lysosome-to-nucleus signaling can be directly controlled by several signaling molecules involved in the mTORC1, PKC, and AKT pathways. MiT/TFE family members have attracted much attention owing to their intracellular clearance of pathogenic factors in numerous diseases. Recently, multiple studies have also revealed the MiT/TFE proteins as master regulators of cellular metabolic reprogramming, converging on autophagic and lysosomal function and playing a critical role in cancer, suggesting that novel therapeutic strategies could be based on the modulation of MiT/TFE family member activity. Here, we present an overview of the latest research on MiT/TFE transcriptional factors and their potential mechanisms in cancer.

Ursodeoxycholic Acid Influences the Expression of p27kip1 but Not FoxO1 in Patients with Non-Cirrhotic Primary Biliary Cirrhosis

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Malgorzata Milkiewicz

2014-01-01

Full Text Available Background. Enhanced expression of cell cycle inhibitor p27kip1 suppresses cell proliferation. Ursodeoxycholic acid (UDCA delays progression of primary biliary cirrhosis (PBC but its effect on p27kip1 expression is uncertain. Aims. To analyze the expression of p27kip1 and its transcription modulator FoxO1 in patients with PBC, and to assess the impact of UDCA on this pathway. Materials and Methods. The examined human tissue included explanted livers from patients with cirrhotic PBC (n=23, primary sclerosing cholangitis (PSC; n=9, alcoholic liver disease (ALD; n=9, and routine liver biopsies from patients with non-cirrhotic PBC (n=26. Healthy liver samples served as controls (n=19. Livers of FoxO-deficient mice were also studied. mRNA and protein expressions were analyzed by real-time PCR and Western blot. Results. p27kip1 expression was increased in cirrhotic and non-cirrhotic PBC. FoxO1 mRNA levels were increased in PBC (8.5-fold increase versus controls. FoxO1 protein expression in PBC was comparable to controls, but it was decreased in patients with PSC and ALD (63% and 70% reduction, respectively; both P<0.05 versus control. UDCA-treated non-cirrhotic patients with PBC showed decreased expression of p27kip1 mRNA. Conclusion. PBC progression is characterized by a FoxO1-independent increase of p27kip1 expression. In early PBC, UDCA may enhance liver regeneration via p27kip1-dependent mechanism.

Proteomic analysis of highly prevalent amyloid A amyloidosis endemic to endangered island foxes.

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Patricia M Gaffney

Full Text Available Amyloid A (AA amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA. Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34% in a genetically isolated population of island foxes (Urocyon littoralis with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%, spleen (58%, oral cavity (45%, and vasculature (44% and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤ 0.05. Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid deposition, a unique SAA sequence, and the co-occurrence of AA with apolipoproteins.

Extracellular Matrix-Regulated Gene Expression RequiresCooperation of SWI/SNF and Transcription Factors

Energy Technology Data Exchange (ETDEWEB)

Xu, Ren; Spencer, Virginia A.; Bissell, Mina J.

2006-05-25

Extracellular cues play crucial roles in the transcriptional regulation of tissue-specific genes, but whether and how these signals lead to chromatin remodeling is not understood and subject to debate. Using chromatin immunoprecipitation (ChIP) assays and mammary-specific genes as models, we show here that extracellular matrix (ECM) molecules and prolactin cooperate to induce histone acetylation and binding of transcription factors and the SWI/SNF complex to the {beta}- and ?-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both {beta}- and ?-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. ChIP analyses demonstrated that the ATPase activity of SWI/SNF is necessary for recruitment of RNA transcriptional machinery, but not for binding of transcription factors or for histone acetylation. Coimmunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, C/EBP{beta}, and glucocorticoid receptor (GR). Thus, ECM- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.

WHEN AND WHY DO HEDGEHOGS AND FOXES DIFFER?

Science.gov (United States)

Keil, Frank C

2010-01-01

Philip E. Tetlock's finding that "hedgehog" experts (those with one big theory) are worse predictors than "foxes" (those with multiple, less comprehensive theories) offers fertile ground for future research. Are experts as likely to exhibit hedgehog- or fox-like tendencies in areas that call for explanatory, diagnostic, and skill-based expertise-as they did when Tetlock called on experts to make predictions? Do particular domains of expertise curtail or encourage different styles of expertise? Can we trace these different styles to childhood? Finally, can we nudge hedgehogs to be more like foxes? Current research can only grope at the answers to these questions, but they are essential to gauging the health of expert political judgment.

The FOX transcription factor Hcm1 regulates oxidative metabolism in response to early nutrient limitation in yeast. Role of Snf1 and Tor1/Sch9 kinases.

Science.gov (United States)

Rodríguez-Colman, María José; Sorolla, M Alba; Vall-Llaura, Núria; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

2013-08-01

Within Saccharomyces cerevisiae, Hcm1is a member of the forkhead transcription factor family with a role in chromosome organization. Our group recently described its involvement in mitochondrial biogenesis and stress resistance, and reports here that Hcm1 played a role in adaptation to respiratory metabolism when glucose or nitrogen was decreased. Regulation of Hcm1 activity occurs in at least three ways: i) protein quantity, ii) subcellular localization, and iii) transcriptional activity. Transcriptional activity was measured using a reporter gene fused to a promoter that contains a binding site for Hcm1. We also analyzed the levels of several genes whose expression is known to be regulated by Hcm1 levels and the role of the main kinases known to respond to nutrients. Lack of sucrose-nonfermenting (Snf1) kinase increases cytoplasmic localization of Hcm1, whereas Δtor1 cells showed a mild increase in nuclear Hcm1. In vitro experiments showed that Snf1 clearly phosphorylates Hcm1 while Sch9 exerts a milder phosphorylation. Although in vitroTor1 does not directly phosphorylate Hcm1, in vivo rapamycin treatment increases nuclear Hcm1. We conclude that Hcm1 participates in the adaptation of cells from fermentation to respiratory metabolism during nutrient scarcity. According to our hypothesis, when nutrient levels decrease, Snf1 phosphorylates Hcm1. This results in a shift from the cytoplasm to the nucleus and increased transcriptional activity of genes involved in respiration, use of alternative energy sources, NAD synthesis and oxidative stress resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

Spontaneous rickets in the wild arctic fox Alopex lagopus

International Nuclear Information System (INIS)

Ogden, J.A.; Conlogue, G.J.

1981-01-01

Normal and rachitic, skeletally immature arctic foxes (Alopex lagopus) were subjected to physical examination, roentgenographic studies, and in some cases histologic studies. The involved animals had active rickets coupled with antecedent normal diaphyseal bone formation. Evaluation of all the long bones showed highly variable manifestations of the disease, which undoubtedly reflect different rates of physeal endochondral transformation and metaphyseal remodeling. Histologic examination showed distinct patterns of widening of the physes and variable osteodystrophy in the trabecular and cortical bone of the metaphyses and epiphyseal ossification centers. These aforementioned factors certainly would necessitate different regional calcium needs and, therefore, different regional responses to an overall calcium deficiency. The physes involved in the most rapid growth rates in this period showed the most widening of the growth plate, and the most dystrophic changes in the metaphysis. Skeletal injuries, including metaphyseal fractures and slow-down of longitudinal growth (particularly in the ulna) were also evident. Because of apparent dietary differences in the affected and normal fox kits, this juvenile-onset disease was presumed due to calcium-deficient intake following weaning. To the best of our knowledge this is the first report of spontaneously occurring rickets in a wild animal in its natural habitat. There are several possible mechanisms for the variable widening of the physis and the loss of bone mineralization in these fox kits: calcium-deficient diet, binding of calcium in the bowel by high phosphorus intake, secondary hyperparathyroidism, and vitamin A toxicity. (orig.)

Physical interactions among plant MADS-box transcription factors and their biological relevance

NARCIS (Netherlands)

Nougalli Tonaco, I.A.

2008-01-01

The biological interpretation of the genome starts from transcription, and many different signaling pathways are integrated at this level. Transcription factors play a central role in the transcription process, because they select the down-stream genes and determine their spatial and temporal

Cooperative binding of transcription factors promotes bimodal gene expression response.

Directory of Open Access Journals (Sweden)

Pablo S Gutierrez

Full Text Available In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is the first report to show that the cooperative binding of transcription factors to DNA promotes the "all-or-none" phenomenon observed in eukaryotic systems. In addition, we confirm that gene expression fluctuation levels associated with one of two cooperative binding mechanism never exceed the fluctuation levels of the other.

A deeper look into transcription regulatory code by preferred pair distance templates for transcription factor binding sites

KAUST Repository

Kulakovskiy, Ivan V.

2011-08-18

Motivation: Modern experimental methods provide substantial information on protein-DNA recognition. Studying arrangements of transcription factor binding sites (TFBSs) of interacting transcription factors (TFs) advances understanding of the transcription regulatory code. Results: We constructed binding motifs for TFs forming a complex with HIF-1α at the erythropoietin 3\\'-enhancer. Corresponding TFBSs were predicted in the segments around transcription start sites (TSSs) of all human genes. Using the genome-wide set of regulatory regions, we observed several strongly preferred distances between hypoxia-responsive element (HRE) and binding sites of a particular cofactor protein. The set of preferred distances was called as a preferred pair distance template (PPDT). PPDT dramatically depended on the TF and orientation of its binding sites relative to HRE. PPDT evaluated from the genome-wide set of regulatory sequences was used to detect significant PPDT-consistent binding site pairs in regulatory regions of hypoxia-responsive genes. We believe PPDT can help to reveal the layout of eukaryotic regulatory segments. © The Author 2011. Published by Oxford University Press. All rights reserved.

A meiotic linkage map of the silver fox, aligned and compared to the canine genome.

Science.gov (United States)

Kukekova, Anna V; Trut, Lyudmila N; Oskina, Irina N; Johnson, Jennifer L; Temnykh, Svetlana V; Kharlamova, Anastasiya V; Shepeleva, Darya V; Gulievich, Rimma G; Shikhevich, Svetlana G; Graphodatsky, Alexander S; Aguirre, Gustavo D; Acland, Gregory M

2007-03-01

A meiotic linkage map is essential for mapping traits of interest and is often the first step toward understanding a cryptic genome. Specific strains of silver fox (a variant of the red fox, Vulpes vulpes), which segregate behavioral and morphological phenotypes, create a need for such a map. One such strain, selected for docility, exhibits friendly dog-like responses to humans, in contrast to another strain selected for aggression. Development of a fox map is facilitated by the known cytogenetic homologies between the dog and fox, and by the availability of high resolution canine genome maps and sequence data. Furthermore, the high genomic sequence identity between dog and fox allows adaptation of canine microsatellites for genotyping and meiotic mapping in foxes. Using 320 such markers, we have constructed the first meiotic linkage map of the fox genome. The resulting sex-averaged map covers 16 fox autosomes and the X chromosome with an average inter-marker distance of 7.5 cM. The total map length corresponds to 1480.2 cM. From comparison of sex-averaged meiotic linkage maps of the fox and dog genomes, suppression of recombination in pericentromeric regions of the metacentric fox chromosomes was apparent, relative to the corresponding segments of acrocentric dog chromosomes. Alignment of the fox meiotic map against the 7.6x canine genome sequence revealed high conservation of marker order between homologous regions of the two species. The fox meiotic map provides a critical tool for genetic studies in foxes and identification of genetic loci and genes implicated in fox domestication.

Specification of jaw identity by the Hand2 transcription factor

Science.gov (United States)

Funato, Noriko; Kokubo, Hiroki; Nakamura, Masataka; Yanagisawa, Hiromi; Saga, Yumiko

2016-01-01

Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel’s cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate. PMID:27329940

In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters.

OpenAIRE

Buckley, SM; Delhove, JM; Perocheau, DP; Karda, R; Rahim, AA; Howe, SJ; Ward, NJ; Birrell, MA; Belvisi, MG; Arbuthnot, P; Johnson, MR; Waddington, SN; McKay, TR

2015-01-01

The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruse...

Multi-population comparison of resource exploitation by island foxes: Implications for conservation

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B.L. Cypher

2014-12-01

Full Text Available Imperiled island foxes are inherently resource-limited by their insular ecology. We examined food use on all 6 islands where they occur to assess resource exploitation patterns. Over 40 different food items were identified with item use varying among islands. Sixteen items occurred with ≥10% frequency in annual fox diets: deer mice, birds, lizards, beetles, beetle larvae, Jerusalem crickets, silk-spinning sand crickets, grasshoppers, earwigs, snails, and fruits of toyon, manzanita, prickly pear cactus, ice plant, Australian saltbush, and summer holly. Foxes used a diversity of food items with variations among islands attributable to island-specific availabilities. Deer mice in particular appeared to be preferred. Foxes also exhibited extensive use of non-native items, such as ice plant fruits, European snails, and earwigs, and foxes may even be dependent on these items on some islands. To increase food security and promote population stability, we recommend (1 continuing and enhancing habitat restoration efforts on all islands, (2 increasing the abundance of native items in association with any removals of non-native species used by foxes, and (3 monitoring annual trends in abundance of key food items as well as periodic monitoring of item use by foxes to determine functional responses to changes in item availability. Keywords: Channel islands, Endangered species, Food-item selection, Foraging ecology, Island fox, Urocyon littoralis

Synthetic Polypeptide Derived from Viral Macrophage Inflammatory ...

African Journals Online (AJOL)

CXCR4 downstream signaling pathways and how they contribute to disease progression. FoxO3a is a member of the FoxO subfamily of forkhead (fox) transcription factors, and the induction of FOXO3a results in the activation of the apoptotic intrinsic (via Bim) and extrinsic (via. FasL and TRAIL) pathways [19]. In this present.

Autochthonous Hepatozoon infection in hunting dogs and foxes from the Czech Republic.

Science.gov (United States)

Mitková, Barbora; Hrazdilová, Kristýna; Steinbauer, Vladimír; D'Amico, Gianluca; Mihalca, Andrei Daniel; Modrý, David

2016-11-01

Blood samples from 21 red foxes (Vulpes vulpes) and 8 hunting dogs from the same locality in the Czech Republic were examined for presence of Hepatozoon canis/Hepatozoon sp. The dogs were selected based on their close contact with foxes during fox bolting and because they had not traveled into known endemic areas. Using diagnostic PCR amplifying partial 18S rDNA fragment, Hepatozoon DNA was detected in 20 red foxes (95 %) and 4 dogs (50 %). From 8 positive foxes and 2 positive dogs, we obtained nearly complete 18S rDNA sequences. Phylogenetic analyses of these sequences revealed very low variability. Buffy coat smears from positive dogs were prepared and examined. No Hepatozoon gamonts were found. This study provides the first report of autochthonous infection of H. canis/Hepatozoon in dogs and foxes from the Czech Republic. Our study indirectly demonstrates cross infection between red foxes and dogs and confirms autochthonous infection of Hepatozoon canis in dogs living in a geographic area well outside the range of Rhipicephalus sanguineus sensu lato, which is so far the only known vector of H. canis in Europe.

Strand transfer and elongation of HIV-1 reverse transcription is facilitated by cell factors in vitro.

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David Warrilow

Full Text Available Recent work suggests a role for multiple host factors in facilitating HIV-1 reverse transcription. Previously, we identified a cellular activity which increases the efficiency of HIV-1 reverse transcription in vitro. Here, we describe aspects of the activity which shed light on its function. The cellular factor did not affect synthesis of strong-stop DNA but did improve downstream DNA synthesis. The stimulatory activity was isolated by gel filtration in a single fraction of the exclusion volume. Velocity-gradient purified HIV-1, which was free of detectable RNase activity, showed poor reverse transcription efficiency but was strongly stimulated by partially purified cell proteins. Hence, the cell factor(s did not inactivate an RNase activity that might degrade the viral genomic RNA and block completion of reverse transcription. Instead, the cell factor(s enhanced first strand transfer and synthesis of late reverse transcription suggesting it stabilized the reverse transcription complex. The factor did not affect lysis of HIV-1 by Triton X-100 in the endogenous reverse transcription (ERT system, and ERT reactions with HIV-1 containing capsid mutations, which varied the biochemical stability of viral core structures and impeded reverse transcription in cells, showed no difference in the ability to be stimulated by the cell factor(s suggesting a lack of involvement of the capsid in the in vitro assay. In addition, reverse transcription products were found to be resistant to exogenous DNase I activity when the active fraction was present in the ERT assay. These results indicate that the cell factor(s may improve reverse transcription by facilitating DNA strand transfer and DNA synthesis. It also had a protective function for the reverse transcription products, but it is unclear if this is related to improved DNA synthesis.

Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo

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Daisuke Kajimura

2014-10-01

Full Text Available The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1Dbh−/− display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1Dbh−/− mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

Science.gov (United States)

Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

2016-06-24

Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

Characterization of senscence-associated NAC transcription factors in Barley (Hordeum Vulgare L.)

DEFF Research Database (Denmark)

Podzimska, Dagmara Agata

, such as yield, biomass production and nutrient quality, and NAC (NAM, ATAF1/2 and CUC2) transcription factors are promising targets for the breeding. The aim of this thesis was thus to assess the role of NAC transcription factors in regulation of senescence in barley (Hordeum vulgare L.) and to contribute...

A behavioral audiogram of the red fox (Vulpes vulpes).

Science.gov (United States)

Malkemper, E Pascal; Topinka, Václav; Burda, Hynek

2015-02-01

We determined the absolute hearing sensitivity of the red fox (Vulpes vulpes) using an adapted standard psychoacoustic procedure. The animals were tested in a reward-based go/no-go procedure in a semi-anechoic chamber. At 60 dB sound pressure level (SPL) (re 20 μPa) red foxes perceive pure tones between 51 Hz and 48 kHz, spanning 9.84 octaves with a single peak sensitivity of -15 dB at 4 kHz. The red foxes' high-frequency cutoff is comparable to that of the domestic dog while the low-frequency cutoff is comparable to that of the domestic cat and the absolute sensitivity is between both species. The maximal absolute sensitivity of the red fox is among the best found to date in any mammal. The procedure used here allows for assessment of animal auditory thresholds using positive reinforcement outside the laboratory. Copyright © 2014 Elsevier B.V. All rights reserved.

The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

Science.gov (United States)

O’Brown, Zach K.; Van Nostrand, Eric L.; Higgins, John P.; Kim, Stuart K.

2015-01-01

Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID:26678048

Problem-Solving Test: The Mechanism of Transcription Termination by the Rho Factor

Science.gov (United States)

Szeberenyi, Jozsef

2012-01-01

Transcription termination comes in two forms in "E. coli" cells. Rho-dependent termination requires the binding of a termination protein called Rho factor to the transcriptional machinery at the terminator region, whereas Rho-independent termination is achieved by conformational changes in the transcript itself. This article presents a test…

75 FR 31510 - Fox Chase Bancorp, Inc., Hatboro, PA; Approval of Conversion

Science.gov (United States)

2010-06-03

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision [AC-43: OTS No. H-4707] Fox Chase Bancorp, Inc., Hatboro, PA; Approval of Conversion Application Notice is hereby given that on May 14, 2010, the Office of Thrift Supervision approved the application of Fox Chase MHC and Fox Chase Bank, Hatboro...

Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice

Science.gov (United States)

Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly; Salim, Angela A; Mamidyala, Sreeman; Butler, Mark S; Robinson, Ashley S; Lesieur, Emmanuelle; Johnston, Wayne; Alexandrov, Kirill; Black, Brian L; Hogan, Benjamin M; De Val, Sarah; Capon, Robert J; Carroll, Jason S; Bailey, Timothy L; Koopman, Peter; Jauch, Ralf; Smyth, Mark J; Cooper, Matthew A; Gambin, Yann; Francois, Mathias

2017-01-01

Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics. DOI: http://dx.doi.org/10.7554/eLife.21221.001 PMID:28137359

Mitochondrial transcription factor A protects human retinal ...

African Journals Online (AJOL)

Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were ...

Differential effects of coyotes and red foxes on duck nest success

Science.gov (United States)

Sovada, Marsha A.; Sargeant, A.; Grier, J.W.

1995-01-01

Low recruitment rates prevail among ducks in the Prairie Pothole Region of North America, primarily because of high nest depredation rates. The red fox (Vulpes vulpes) is a major predator of duck eggs, but fox abundance is depressed by coyotes (Canis latrans). We tested the hypothesis that nest success of upland-nesting ducks is higher in areas with coyotes than in areas with red foxes. We conducted the study during 1990-92 in uplands of 36 areas managed for nesting ducks in North Dakota and South Dakota. Overall nest success averaged 32% (95% CI = 25-40) on 17 study areas where coyotes were the principal canid and 17% (CI = 11-25) on 13 study areas where red foxes were the principal canid (P = 0.01). Both canids were common on 6 other areas, where nest success averaged 25% (CI = 13-47). Habitat composition, predator communities with the exception of canids, and species composition of duck nests in coyote and red fox areas were similar overall. Upon examining only nests with greater than or equal to 6 eggs on the last visit prior to hatch or depredation, we determined nests with evidence characteristic of fox predation accounted for 4% of depredated nests in coyote areas and 27% in fox areas (P = 0.001). An expanding coyote population is contributing to higher overall nest success. Management of coyotes may be an effective method for increasing duck nest success.

Proteopedia: 3D Visualization and Annotation of Transcription Factor-DNA Readout Modes

Science.gov (United States)

Dantas Machado, Ana Carolina; Saleebyan, Skyler B.; Holmes, Bailey T.; Karelina, Maria; Tam, Julia; Kim, Sharon Y.; Kim, Keziah H.; Dror, Iris; Hodis, Eran; Martz, Eric; Compeau, Patricia A.; Rohs, Remo

2012-01-01

3D visualization assists in identifying diverse mechanisms of protein-DNA recognition that can be observed for transcription factors and other DNA binding proteins. We used Proteopedia to illustrate transcription factor-DNA readout modes with a focus on DNA shape, which can be a function of either nucleotide sequence (Hox proteins) or base pairing…

Endoparasites of the raccoon dog (Nyctereutes procyonoides) and the red fox (Vulpes vulpes) in Denmark 2009–2012 – A comparative study

Science.gov (United States)

Al-Sabi, Mohammad Nafi Solaiman; Chriél, Mariann; Jensen, Trine Hammer; Enemark, Heidi Larsen

2013-01-01

Invasive species negatively influence the biodiversity of the ecosystems they invade and may introduce pathogens to native species. Raccoon dogs have very successfully invaded Europe, including, recently, Denmark. This study included analyses of gastrointestinal helminths and Trichinella spp. from 99 raccoon dogs and 384 native red foxes collected from October 2009 to March 2012. The sedimentation and counting method used revealed that raccoon dogs and foxes harboured 9 and 13 different helminth species, respectively, of which several known to be zoonotic. Significantly more nematode and cestode species were found in foxes while raccoon dogs had more trematode species. Rodent transmitted parasites were more prevalent in foxes, while amphibian transmitted parasites were more prevalent in raccoon dogs. One fox was infected with Echinococcus multilocularis (0.3%), while no Trichinella spp. were detected in raccoon dogs or foxes. The trematode Brachylaima tokudai was detected for the first time in Denmark in five of 384 foxes (1.3%). Prevalences of Pygidiopsis summa (3.0% and 3.4%) and Cryptocotyle spp. (15.2% and 15.4%) were comparable in raccoon dogs and foxes, respectively. Four helminth species were more prevalent in foxes than in raccoon dogs: Toxocara canis (60.9% and 13.1%); Uncinaria stenocephala (84.1% and 48.5%); Mesocestoides spp. (42.7% and 23.2%); and Taenia spp. (30.7% and 2.0%), respectively. Three helminth species were more prevalent in raccoon dogs than in foxes: Dipylidium caninum (5.1% and 0.3%); Mesorchis denticulatus (38.4% and 4.2%); and Alaria alata (69.7% and 34.4%), respectively. T. canis was more abundant in foxes while A. alata was more abundant in raccoon dogs. The intestinal distribution of a number of helminth species was comparable between hosts, but highly variable between parasite species. Inherent biological factors and host invasion of new areas might have shaped these marked differences in helminth fauna between the invasive raccoon

Expression of fox-related genes in the skin follicles of Inner Mongolia cashmere goat

OpenAIRE

Wenjing Han; Xiaoyan Li; Lele Wang; Honghao Wang; Kun Yang; Zhixin Wang; Ruijun Wang; Rui Su; Zhihong Liu; Yanhong Zhao; Yanjun Zhang; Jinquan Li

2018-01-01

Objective This study investigated the expression of genes in cashmere goats at different periods of their fetal development. Methods Bioinformatics analysis was used to evaluate data obtained by transcriptome sequencing of fetus skin samples collected from Inner Mongolia cashmere goats on days 45, 55, and 65 of fetal age. Results We found that FoxN1, FoxE1, and FoxI3 genes of the Fox gene family were probably involved in the growth and development of the follicle and the formation of hair, wh...

E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

Directory of Open Access Journals (Sweden)

David G. Johnson

2012-10-01

Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP.

Science.gov (United States)

Elkord, Eyad; Abd Al Samid, May; Chaudhary, Belal

2015-08-21

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.

Arabidopsis R2R3-MYB transcription factor AtMYB60 functions as a transcriptional repressor of anthocyanin biosynthesis in lettuce (Lactuca sativa).

Science.gov (United States)

Park, Jong-Sug; Kim, Jung-Bong; Cho, Kang-Jin; Cheon, Choong-Ill; Sung, Mi-Kyung; Choung, Myoung-Gun; Roh, Kyung-Hee

2008-06-01

The MYB transcription factors play important roles in the regulation of many secondary metabolites at the transcriptional level. We evaluated the possible roles of the Arabidopsis R2R3-MYB transcription factors in flavonoid biosynthesis because they are induced by UV-B irradiation but their associated phenotypes are largely unexplored. We isolated their genes by RACE-PCR, and performed transgenic approach and metabolite analyses in lettuce (Lactuca sativa). We found that one member of this protein family, AtMYB60, inhibits anthocyanin biosynthesis in the lettuce plant. Wild-type lettuce normally accumulates anthocyanin, predominantly cyanidin and traces of delphinidin, and develops a red pigmentation. However, the production and accumulation of anthocyanin pigments in AtMYB60-overexpressing lettuce was inhibited. Using RT-PCR analysis, we also identified the complete absence or reduction of dihydroflavonol 4-reductase (DFR) transcripts in AtMYB60- overexpressing lettuce (AtMYB60-117 and AtMYB60-112 lines). The correlation between the overexpression of AtMYB60 and the inhibition of anthocyanin accumulation suggests that the transcription factorAtMYB60 controls anthocyanin biosynthesis in the lettuce leaf. Clarification of the roles of the AtMYB60 transcription factor will facilitate further studies and provide genetic tools to better understand the regulation in plants of the genes controlled by the MYB-type transcription factors. Furthermore, the characterization of AtMYB60 has implications for the development of new varieties of lettuce and other commercially important plants with metabolic engineering approaches.

The mitochondrial transcription factor A functions in mitochondrial base excision repair

DEFF Research Database (Denmark)

Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V

2010-01-01

Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected i...

Interaction between FMDV Lpro and transcription factor ADNP is required for viral replication

Science.gov (United States)

The foot-and-mouth disease virus (FMDV) leader protease (Lpro) inhibits host translation and transcription affecting the expression of several factors involved in innate immunity. In this study, we have identified the host transcription factor ADNP (activity dependent neuroprotective protein) as an ...

Genome organization and DNA methylation patterns of B chromosomes in the red fox and Chinese raccoon dogs.

Science.gov (United States)

Bugno-Poniewierska, Monika; Solek, Przemysław; Wronski, Mariusz; Potocki, Leszek; Jezewska-Witkowska, Grażyna; Wnuk, Maciej

2014-12-01

The molecular structure of B chromosomes (Bs) is relatively well studied. Previous research demonstrates that Bs of various species usually contain two types of repetitive DNA sequences, satellite DNA and ribosomal DNA, but Bs also contain genes encoding histone proteins and many others. However, many questions remain regarding the origin and function of these chromosomes. Here, we focused on the comparative cytogenetic characteristics of the red fox and Chinese raccoon dog B chromosomes with particular attention to the distribution of repetitive DNA sequences and their methylation status. We confirmed that the small Bs of the red fox show a typical fluorescent telomeric distal signal, whereas medium-sized Bs of the Chinese raccoon dog were characterized by clusters of telomeric sequences along their length. We also found different DNA methylation patterns for the B chromosomes of both species. Therefore, we concluded that DNA methylation may maintain the transcriptional inactivation of DNA sequences localized to B chromosomes and may prevent genetic unbalancing and several negative phenotypic effects. © 2014 The Authors.

WRKY transcription factor superfamily: Structure, origin and functions

African Journals Online (AJOL)

terminal ends contain the WRKYGQR amino acid sequence and a zinc-finger motif. WRKY transcription factors can regulate the expression of target genes that contain the W-box elements (C/T)TGAC(C/T) in the promoter regions by specifically ...

Posttranslational modifications of Forkhead box O transcription factors

NARCIS (Netherlands)

Horst, Aart Arno van der

2006-01-01

FOXO transcription factors play an important role in essential biological processes such as differentiation, proliferation, apoptosis, DNA repair, metabolism and stress resistance. Phosphorylation is the modification that was first found on FOXOs and much of the subsequent studies focused on this

Food composition and feeding ecology of the Red Fox Vulpes ...

African Journals Online (AJOL)

Food composition of the Red Fox Vulpes vulpes populations in different habitats in Egypt is ..... The dietary choices of small carnivores such as the Red Fox will depend primarily ... Similarly, feeding on carrion would be most cost effective. The.

Group A Rotavirus Associated with Encephalitis in Red Fox.

Science.gov (United States)

Busi, Chiara; Martella, Vito; Papetti, Alice; Sabelli, Cristiano; Lelli, Davide; Alborali, G Loris; Gibelli, Lucia; Gelmetti, Daniela; Lavazza, Antonio; Cordioli, Paolo; Boniotti, M Beatrice

2017-09-01

In 2011, a group A rotavirus was isolated from the brain of a fox with encephalitis and neurologic signs, detected by rabies surveillance in Italy. Intracerebral inoculation of fox brain homogenates into mice was fatal. Genome sequencing revealed a heterologous rotavirus of avian origin, which could provide a model for investigating rotavirus neurovirulence.

Transcription factor trapping by RNA in gene regulatory elements.

Science.gov (United States)

Sigova, Alla A; Abraham, Brian J; Ji, Xiong; Molinie, Benoit; Hannett, Nancy M; Guo, Yang Eric; Jangi, Mohini; Giallourakis, Cosmas C; Sharp, Phillip A; Young, Richard A

2015-11-20

Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs. Copyright © 2015, American Association for the Advancement of Science.

G =  MAT: linking transcription factor expression and DNA binding data.

Science.gov (United States)

Tretyakov, Konstantin; Laur, Sven; Vilo, Jaak

2011-01-31

Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/.

G = MAT: Linking Transcription Factor Expression and DNA Binding Data

Science.gov (United States)

Tretyakov, Konstantin; Laur, Sven; Vilo, Jaak

2011-01-01

Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/. PMID:21297945

Mechanism of transcription activation at the comG promoter by the competence transcription factor ComK of Bacillus subtilis

NARCIS (Netherlands)

Susanna, KA; van der Werff, AF; den Hengst, CD; Calles, B; Salas, M; Venema, G; Hamoen, LW; Kuipers, OP

The development of genetic competence in Bacillus subtilis is regulated by a complex signal transduction cascade, which results in the synthesis of the competence transcription factor, encoded by comK. ComK is required for the transcription of the late competence genes that encode the DNA binding

Red fox spatial characteristics in relation to waterfowl predation

Science.gov (United States)

Sargeant, A.B.

1972-01-01

Radio-equipped red foxes (Vulpes vulpes) on the Cedar Creek area in Minnesota were spatially distributed, with individual families occupying well defined, nonoverlapping, contiguous territories. Territory boundaries often conformed to natural physical boundaries and appeared to be maintained through some nonaggressive behavior mechanism. Individual foxes traveled extensively throughout the family territory each night. Fox territories appeared to range from approximately 1 to 3 square miles in size, dependent largely on population density. Red foxes used a sequence of dens to rear their pups, and the amount and location of food remains at individual dens changed as the pups matured. The denning season was divided into pre-emergence, confined-use, and dispersed-use periods of 4 to 5 weeks each. Remains of adult waterfowl were collected at rearing dens on six townships in three ecologically different regions of eastern North Dakota. Remains of 172 adult dabbling ducks and 16 adult American coots (Fulica americana) were found at 35 dens. No remains from diving ducks were found. The number of adult ducks per den averaged 1.6, 5.9, and 10.2 for paired townships in regions with relatively low, moderate and high duck populations, respectively. Eighty-four percent of the ducks were females. The species and sex composition of ducks found at dens during early and late sampling periods reflected the nesting chronology of prairie dabbling ducks. Occupied rearing dens were focal points of red fox travel, and the locations of dens may have had considerable influence on predation. Thirty-five of 38 dens found on the six township study areas were on pastured or idle lands. The distribution of rearing dens on the Sand Lake and Arrowwood national wildlife refuges suggested that, on these areas, fox dens were concentrated because of the topography and land-use practices.

Genetic diversity and phylogeny of the Christmas Island flying fox (Pteropus melanotus natalis)

Czech Academy of Sciences Publication Activity Database

Phalen, D. N.; Hall, J.; Ganesh, G.; Hartigan, Ashlie; Smith, C.; De Jong, C.; Field, H.; Rose, K.

2017-01-01

Roč. 98, č. 2 (2017), s. 428-437 ISSN 0022-2372 Institutional support: RVO:60077344 Keywords : diversity * flying fox * mitochondrial DNA * phylogeny * Pteropus melanotus natalis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 1.630, year: 2016

[Comparison of fluoride concentrations in human, dog, fox and raccoon dog bones from northwestern Poland].

Science.gov (United States)

Palczewska-Komsa, Mirona

2015-01-01

Since the beginning of the XXth there has been a constant increase in fluoride (F-) emissions into the environment, mainly due to the development of industry, the fluoridation of drinking water, and the widespread use of toothpaste containing fluoride. All these factors have resulted in an intensive accumulation of F- in the bodies of vertebrates, mainly in their bones. It is therefore reasonable to estimate the F- concentration in humans and other long-lived mammals. Accordingly, ecotoxicologists worldwide have looked for mammalian species that may serve as good bioindicators of environmental fluoride pollution. In contrast to ungulates, long-lived domestic mammals and wild carnivores have rarely been used for this purpose (including the dog, fox and raccoon dog). The main aims of this study were to: 1) investigate F- concentrations in bones obtained from humans, dog, fox and raccoon dog from northwestern Poland, 2) perform intra- and inter-specific comparisons of F- concentrations in the studied mammalian bones against the background of environmental and living conditions, 3) examine the relationship between concentrations of F- in bones and the age or age category of the studied mammals. The study material comprised bones of the hip joint obtained from 36 patients who underwent hip replacement in Szczecin, 43 dogs from Szczecin veterinary clinics, 32 foxes and 18 raccoon dogs provided by hunters, with the whole test material consisting of 129 samples. The indications of F- (using potentiometry with Thermo Orion ion-selective electrodes) were performed in triplicate. The F- concentration was expressed on a dry weight basis. Interspecific analysis showed that the largest number of differences in the concentrations of F- were between the fox and raccoon, and then between the dog and fox, and then between the dog and the wild canids (foxes and raccoon dogs together). Close statistically significant differences were also found between the samples from humans and the

Habitat selection and diurnal refugia of gray foxes in southwestern Georgia, USA.

Directory of Open Access Journals (Sweden)

Nicholas R Deuel

Full Text Available Understanding habitat selection of gray foxes (Urocyon cinereoargenteus is essential to evaluate their potential response to changes in land use and predator communities. Few studies have evaluated temporal habitat selection or explicitly identified habitats used by gray foxes for diurnal refugia. We used GPS collars to obtain location data for 34 gray foxes (20 males and 14 females from February 2014 to December 2015 to evaluate temporal (seasonal and diel habitat selection and selection of diurnal refugia in southwestern Georgia, USA. We analyzed habitat selection at 2 levels, selection of a core area within the home range and selection of locations within the home range. Habitat selection was non-random (P 0.05. Hardwoods, human use (i.e., areas associated with regular human activity such as buildings, lawns, parking areas, etc., and roads were selected (P 0.05. Selection of habitats for diurnal refugia did not vary seasonally or by sex (P > 0.05, with foxes selecting (P < 0.05 areas near hardwood forests, roads, agriculture, human use, pastures/food plots, and shrub scrub habitats. Gray foxes were observed on the ground while resting, and we found no evidence of gray foxes diurnally resting in trees. Our results suggest that on our study area, gray foxes are an edge species that prefer forests with a hardwood component in areas near human use and roads.

A gene regulatory network controlling hhex transcription in the anterior endoderm of the organizer

Science.gov (United States)

Rankin, Scott A.; Kormish, Jay; Kofron, Matt; Jegga, Anil; Zorn, Aaron M.

2011-01-01

The homeobox gene hhex is one of the earliest markers of the anterior endoderm, which gives rise to foregut organs such as the liver, ventral pancreas, thyroid, and lungs. The regulatory networks controlling hhex transcription are poorly understood. In an extensive cis-regulatory analysis of the Xenopus hhex promoter we determined how the Nodal, Wnt, and BMP pathways and their downstream transcription factors regulate hhex expression in the gastrula organizer. We show that Nodal signaling, present throughout the endoderm, directly activates hhex transcription via FoxH1/Smad2 binding sites in the proximal −0.44 Kb promoter. This positive action of Nodal is suppressed in the ventral-posterior endoderm by Vent 1 and Vent2, homeodomain repressors that are induced by BMP signaling. Maternal Wnt/β-catenin on the dorsal side of the embryo cooperates with Nodal and indirectly activate hhex expression via the homeodomain activators Siamois and Twin. Siamois/Twin stimulate hhex transcription through two mechanisms: 1) They induce the expression of Otx2 and Lim1 and together Siamois, Twin, Otx2 and Lim1 appear to promote hhex transcription through homeobox sites in a Wnt-responsive element located between −0.65 to −0.55 Kb of the hhex promoter. 2) Siamois/Twin also induce the expression of the BMP-antagonists Chordin and Noggin, which are required to exclude Vents from the organizer allowing hhex transcription. This work reveals a complex network regulating anterior endoderm transcription in the early embryo. PMID:21215263

[Relationship between FoxO1 Expression and Wound Age during Skin Incised Wound Healing].

Science.gov (United States)

Chen, Y; Ji, X Y; Fan, Y Y; Yu, L S

2018-02-01

To investigate FoxO1 expression and its time-dependent changes during the skin incised wound healing. After the establishment of the skin incised wound model in mice, the FoxO1 expression of skin in different time periods was detected by immunohistochemistry and Western blotting. Immunohistochemistry staining showed that FoxO1 was weakly expressed in a few fibroblasts of epidermis, hair follicles, sebaceous glands, vessel endothelium and dermis in the control group. The FoxO1 expression was enhanced in the epidermis and skin appendages around the wound during 6-12 h after injury, which could be detected in the infiltrating neutrophils and a small number of monocytes. FoxO1 was mainly expressed in monocytes during 1-3 d after injury, and in neovascular endothelial cells and fibroblasts during 5-10 d. On the 14th day after injury, the FoxO1 expression still could be detected in a few fibroblasts. The Western blotting results showed that the FoxO1 expression quantity of the tissue samples in injury group was higher than in control group. The FoxO1 expression peaked at 12 h and 7 d after injury. FoxO1 is time-dependently expressed in skin wound healing, which can be a useful marker for wound age determination. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Evaluation of fox tail millet (Setaria italica forage quality in different growth stages

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F. Izadi Yazdanabadi

2016-05-01

Full Text Available In order to evaluate the quantitative factors in fox tail millet (Setaria italica L. under three stages of growth, an experiment was conducted in Birjand during spring and summer of 2010. The preliminary objective was evaluation of fox tail physiological characteristics on animals that feed them. Planting of Foxtail millet was performed according to local practices and endemic acknowledge. Sampling was carried out at Vegetative, flowering and seeding stages, then samples transported to laboratory of animal nutrition. After Drying of sampling, dry matter, dry matter digestibility, crude protein, metabolically energy, Acid Detergent Fiber and Nitrogen Detergent Fiber, Ash and some mineral nutrients were measured. The results showed significant differences in measured characteristics in various phonological stages. Forage quality was higher in flowering and seeding stages than in vegetative stage. Dry matter digestibility and metabolically energy were high and NDF and ADF were less in vegetative stage. Because fox tail millet is leafy and palatable by animal at this stage, it’s optimum yield is important. Ability to produce Green fodder by this plant and the possibility of cultivation in different regions and its ability to produce forage for livestocks, its planting is recommended.

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

OpenAIRE

In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A

1997-01-01

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, delet...

G =  MAT: linking transcription factor expression and DNA binding data.

Directory of Open Access Journals (Sweden)

Konstantin Tretyakov

Full Text Available Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/.

THE RELATIONSHIP OF FoxP3+ T REGULATORY CELLS TO DISEASE ACTIVITY AND ANTIBODY LEVELS IN EARLY RHEUMATOID ARTHRITIS

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A. S. Avdeeva

2017-01-01

Full Text Available Objective: to analyze the relationship of the count of FoxP3+ T regulatory cells (Tregs to the clinical and laboratory parameters of disease activity and the levels of antibodies in a group of patients with early rheumatoid arthritis (RA.Subjects and methods. The investigation enrolled 45 patients with early RA (2010 ACR/EULAR criteria who had not previously received treatment with methotrexate, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28 5.01 [4.18; 5.8]; 71.1% of the patients were rheumatoid factor (RF positive and 88.9% were anti-cyclic citrullinated peptide positive. The relative and absolute counts of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+ were measured by immunofluorescence staining and multicolor flow cytometry. A control group consisted of 20 healthy donors who were matched for sex and age with the examined patients.Results and discussion. DАS28 was high, moderate, and low in 22 (48.9%, 20 (44.4%, and 3 (6.7% patients, respectively. As compared with the healthy donors, the patients with early RA were observed to have lower values in the percentage of FoxP3+CD25+ cells, in the percentage and absolute count of FoxP3+ICOS+ cells, in the percentage and absolute count of FoxP3+CD154+ and FoxP3+ CD274+ T cells; p<0.05 in all cases. Negative correlation was recorded between the percentage of FoxP3+CD25+ and C-reactive protein (CRP (r=-0.4; that of CD152+intracellular and DAS28 (r=-0.35, ESR (r=-0.46, CRP (r=-0.54; that of FoxP3+CD127 and CRP (r=-0.42; that of CD25+CD127 and DAS28 (r=-0.38, SDAI (r=-0.41, CDAI (r=-0.36, ESR (r=-0.39, CRP (r=-0.47; p<0.05 in all cases.The patients who were seronegative for RF were found to have higher values in the percentage of CD25+CD127, in the percentage and absolute count of Foxp3+CD154+ and Foxp3+CD274+ T lymphocytes.Conclusion. The given data may indicate that the

DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. (research article)

NARCIS (Netherlands)

L. Schaeffer; R. Roy (Richard); S. Humbert; V. Moncollin; W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan); P. Chambon; J-M. Egly (Jean-Marc)

1993-01-01

textabstractThe human BTF2 basic transcription factor (also called TFIIH), which is similar to the delta factor in rat and factor b in yeast, is required for class II gene transcription. A strand displacement assay was used to show that highly purified preparation of BTF2 had an adenosine

Asap: a framework for over-representation statistics for transcription factor binding sites

DEFF Research Database (Denmark)

Marstrand, Troels T; Frellsen, Jes; Moltke, Ida

2008-01-01

-founded choice. METHODOLOGY: We introduce a software package, Asap, for fast searching with position weight matrices that include several standard methods for assessing over-representation. We have compared the ability of these methods to detect over-represented transcription factor binding sites in artificial......BACKGROUND: In studies of gene regulation the efficient computational detection of over-represented transcription factor binding sites is an increasingly important aspect. Several published methods can be used for testing whether a set of hypothesised co-regulated genes share a common regulatory...... regime based on the occurrence of the modelled transcription factor binding sites. However there is little or no information available for guiding the end users choice of method. Furthermore it would be necessary to obtain several different software programs from various sources to make a well...

Flying-foxes in the Australian urban environment—community attitudes and opinions

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Nina Y. Kung

2015-12-01

Full Text Available The urban presence of flying-foxes (pteropid bats in eastern Australia has increased in the last 20 years, putatively reflecting broader landscape change. The influx of large numbers often precipitates community angst, typically stemming from concerns about loss of social amenity, economic loss or negative health impacts from recently emerged bat-mediated zoonotic diseases such as Hendra virus and Australian bat lyssavirus. Local authorities and state wildlife authorities are increasingly asked to approve the dispersal or modification of flying-fox roosts to address expressed concerns, yet the scale of this concern within the community, and the veracity of the basis for concern are often unclear. We conducted an on-line survey to capture community attitudes and opinions on flying-foxes in the urban environment to inform management policy and decision-making. Analysis focused on awareness, concerns, and management options, and primarily compared responses from communities where flying-fox management was and was not topical at the time of the survey. While a majority of respondents indicated a moderate to high level of knowledge of both flying-foxes and Hendra virus, a substantial minority mistakenly believed that flying-foxes pose a direct infection risk to humans, suggesting miscommunication or misinformation, and the need for additional risk communication strategies. Secondly, a minority of community members indicated they were directly impacted by urban roosts, most plausibly those living in close proximity to the roost, suggesting that targeted management options are warranted. Thirdly, neither dispersal nor culling was seen as an appropriate management strategy by the majority of respondents, including those from postcodes where flying-fox management was topical. These findings usefully inform community debate and policy development and demonstrate the value of social analysis in defining the issues and options in this complex human�

Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

Science.gov (United States)

Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

2018-01-15

Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

The transcription factor KLF2 restrains CD4⁺ T follicular helper cell differentiation.

Science.gov (United States)

Lee, June-Yong; Skon, Cara N; Lee, You Jeong; Oh, Soohwan; Taylor, Justin J; Malhotra, Deepali; Jenkins, Marc K; Rosenfeld, M Geoffrey; Hogquist, Kristin A; Jameson, Stephen C

2015-02-17

T follicular helper (Tfh) cells are essential for efficient B cell responses, yet the factors that regulate differentiation of this CD4(+) T cell subset are incompletely understood. Here we found that the KLF2 transcription factor serves to restrain Tfh cell generation. Induced KLF2 deficiency in activated CD4(+) T cells led to increased Tfh cell generation and B cell priming, whereas KLF2 overexpression prevented Tfh cell production. KLF2 promotes expression of the trafficking receptor S1PR1, and S1PR1 downregulation is essential for efficient Tfh cell production. However, KLF2 also induced expression of the transcription factor Blimp-1, which repressed transcription factor Bcl-6 and thereby impaired Tfh cell differentiation. Furthermore, KLF2 induced expression of the transcription factors T-bet and GATA3 and enhanced Th1 differentiation. Hence, our data indicate KLF2 is pivotal for coordinating CD4(+) T cell differentiation through two distinct and complementary mechanisms: via control of T cell localization and by regulation of lineage-defining transcription factors. Copyright © 2015 Elsevier Inc. All rights reserved.

DOT/FAA Human Factors Workshop on Aviation (5th). Transcript.

Science.gov (United States)

1982-01-01

This document is a verbatim transcript of the proceedings of the Fifth Human Factors Workshop held at the Mike Monroney Aeronautical Center in Oklahoma City, Oklahoma, on July 7-9, 1981. The Sixth Human Factors Workshop was held at the same facility ...

Functionally significant, rare transcription factor variants in tetralogy of Fallot.

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Ana Töpf

Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

The transcription factor ATF3 is upregulated during chondrocyte differentiation and represses cyclin D1 and A gene transcription

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James Claudine G

2006-09-01

Full Text Available Abstract Background Coordinated chondrocyte proliferation and differentiation are required for normal endochondral bone growth. Transcription factors binding to the cyclicAMP response element (CRE are known to regulate these processes. One member of this family, Activating Tanscription Factor 3 (ATF3, is expressed during skeletogenesis and acts as a transcriptional repressor, but the function of this protein in chondrogenesis is unknown. Results Here we demonstrate that Atf3 mRNA levels increase during mouse chondrocyte differentiation in vitro and in vivo. In addition, Atf3 mRNA levels are increased in response to cytochalasin D treatment, an inducer of chondrocyte maturation. This is accompanied by increased Atf3 promoter activity in cytochalasin D-treated chondrocytes. We had shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A in chondrocytes is dependent on CREs. Here we demonstrate that overexpression of ATF3 in primary mouse chondrocytes results in reduced transcription of both genes, as well as decreased activity of a CRE reporter plasmid. Repression of cyclin A transcription by ATF3 required the CRE in the cyclin A promoter. In parallel, ATF3 overexpression reduces the activity of a SOX9-dependent promoter and increases the activity of a RUNX2-dependent promoter. Conclusion Our data suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes results in down-regulation of cyclin D1 and cyclin A expression as well as activation of RUNX2-dependent transcription. Therefore, ATF3 induction appears to facilitate cell cycle exit and terminal differentiation of chondrocytes.

Electrochemical investigation of 2,2-dinitroethene-1,1-diamine (FOX-7) in aqueous media

Czech Academy of Sciences Publication Activity Database

Šimková, Ludmila; Klíma, Jiří; Sazama, Petr; Ludvík, Jiří

2011-01-01

Roč. 15, č. 10 (2011), s. 2133-2139 ISSN 1432-8488 R&D Projects: GA MŠk ME09002 Institutional research plan: CEZ:AV0Z40400503 Keywords : 2,2-dinitroethene-11-diamine * FOX -7 * reduction Subject RIV: CG - Electrochemistry Impact factor: 2.131, year: 2011

Transcription factors as readers and effectors of DNA methylation.

Science.gov (United States)

Zhu, Heng; Wang, Guohua; Qian, Jiang

2016-08-01

Recent technological advances have made it possible to decode DNA methylomes at single-base-pair resolution under various physiological conditions. Many aberrant or differentially methylated sites have been discovered, but the mechanisms by which changes in DNA methylation lead to observed phenotypes, such as cancer, remain elusive. The classical view of methylation-mediated protein-DNA interactions is that only proteins with a methyl-CpG binding domain (MBD) can interact with methylated DNA. However, evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA. The identification of these proteins and the elucidation of their characteristics and the biological consequences of methylation-dependent transcription factor-DNA interactions are important stepping stones towards a mechanistic understanding of methylation-mediated biological processes, which have crucial implications for human development and disease.

The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF-16/FOXO transcription factors.

Science.gov (United States)

Ikeda, Takako; Uno, Masaharu; Honjoh, Sakiko; Nishida, Eisuke

2017-08-09

The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16. MYS-1 and TRR-1 are recruited to the promoter regions of the daf-16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes oxidative stress resistance by up-regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to the promoter regions of the foxo1 gene, where it increases H4K16 acetylation levels. Our results thus identify the evolutionarily conserved role of the MYST family acetyltransferase as a key epigenetic regulator of DAF-16/FOXO transcription factors. © 2017 The Authors.

Diversity of Flea (Siphonaptera) Parasites on Red Foxes (Vulpes vulpes) in Romania.

Science.gov (United States)

Foley, P; Foley, J; Sándor, A D; Ionica, A M; Matei, I A; D'Amico, G; Gherman, C M; Dom A, C; Mihalca, A D

2017-09-01

Red foxes (Vulpes vulpes (L.)) are widespread across Europe, tolerant of synanthropic ecosystems, and susceptible to diseases potentially shared with humans and other animals. We describe flea fauna on red foxes in Romania, a large, ecologically diverse country, in part because fleas may serve as an indicator of the risk of spillover of vector-borne disease. We found 912 individual fleas of seven species on the 305 foxes assessed, for an infestation prevalence of 49.5%. Mean flea load per fox was 5.8 (range 0-44 fleas), and flea detections were most abundant in fall and early spring. Fleas included generalists (Ctenocephalides canis (Curtis), 32.6% of all fleas), Ct. felis (Bouché, 0.1%), and Pulex irritans L. (29.9%), the fox specialist Chaetopsylla globiceps (Taschenberg, 32.5%), mesocarnivore fleas Paraceras melis Walker (3.2%) and Ch. trichosa Kohaut (1.5%), and the small mammal flea Ctenophthalmus assimilis (Taschenberg, 0.1%), which is rarely or never reported from carnivores. There were significantly more female than male Ch. globiceps, Ct. canis, and Pu. irritans, and these three species were the most broadly distributed geographically. Diversity indices suggested reduced diversity in mountainous areas above 700 m. When compared to other flea studies on foxes in Europe, Romania had flea diversity near the median of reports, which was unexpected given Romania's high ecological diversity. Notably absent prey specialists, compared to other studies, include Archaeopsylla erinacei (Bouché) and Spilopsyllus cuniculi (Dale). Further studies of possible disease agents in fox fleas could help elucidate possible risks of vector-borne disease in foxes, domestic animals, and humans as well. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Incorporating evolution of transcription factor binding sites into ...

Indian Academy of Sciences (India)

PRAKASH KUMAR

Identifying transcription factor binding sites (TFBSs) is essential to elucidate ... alignments with parts annotated as gap lessly aligned TFBSs (pair-profile hits) are generated. Moreover, the pair- profile related parameters are derived in a sound statistical framework. ... Much research has gone into the study of the evolution of.

Identification of a novel and unique transcription factor in the intraerythrocytic stage of Plasmodium falciparum.

Directory of Open Access Journals (Sweden)

Kanako Komaki-Yasuda

Full Text Available The mechanisms of stage-specific gene regulation in the malaria parasite Plasmodium falciparum are largely unclear, with only a small number of specific regulatory transcription factors (AP2 family having been identified. In particular, the transcription factors that function in the intraerythrocytic stage remain to be elucidated. Previously, as a model case for stage-specific transcription in the P. falciparum intraerythrocytic stage, we analyzed the transcriptional regulation of pf1-cys-prx, a trophozoite/schizont-specific gene, and suggested that some nuclear factors bind specifically to the cis-element of pf1-cys-prx and enhance transcription. In the present study, we purified nuclear factors from parasite nuclear extract by 5 steps of chromatography, and identified a factor termed PREBP. PREBP is not included in the AP2 family, and is a novel protein with four K-homology (KH domains. The KH domain is known to be found in RNA-binding or single-stranded DNA-binding proteins. PREBP is well conserved in Plasmodium species and partially conserved in phylum Apicomplexa. To evaluate the effects of PREBP overexpression, we used a transient overexpression and luciferase assay combined approach. Overexpression of PREBP markedly enhanced luciferase expression under the control of the pf1-cys-prx cis-element. These results provide the first evidence of a novel transcription factor that activates the gene expression in the malaria parasite intraerythrocytic stage. These findings enhance our understanding of the evolution of specific transcription machinery in Plasmodium and other eukaryotes.

Biological effects of tolerable level chronic boron intake on transcription factors.

Science.gov (United States)

Orenay Boyacioglu, Seda; Korkmaz, Mehmet; Kahraman, Erkan; Yildirim, Hatice; Bora, Selin; Ataman, Osman Yavuz

2017-01-01

The mechanism of boron effect on human transcription and translation has not been fully understood. In the current study it was aimed to reveal the role of boron on the expression of certain transcription factors that play key roles in many cellular pathways on human subjects chronically exposed to low amounts of boron. The boron concentrations in drinking water samples were 1.57±0.06mg/l for boron group while the corresponding value for the control group was 0.016±0.002mg/l. RNA isolation was performed using PAX gene RNA kit on the blood samples from the subjects. The RNA was then reverse transcribed into cDNA and analyzed using the Human Transcription Factors RT 2 Profiler™ PCR Arrays. While the boron amount in urine was detected as 3.56±1.47mg/day in the boron group, it was 0.72±0.30mg/day in the control group. Daily boron intake of the boron and control groups were calculated to be 6.98±3.39 and 1.18±0.41mg/day, respectively. The expression levels of the transcription factor genes were compared between the boron and control groups and no statistically significant difference was detected (P>0.05). The data suggest that boron intake at 6.98±3.39mg/day, which is the dose at which beneficial effects might be seen, does not result in toxicity at molecular level since the expression levels of transcription factors are not changed. Although boron intake over this level will seem to increase RNA synthesis, further examination of the topic is needed using new molecular epidemiological data. Copyright © 2016 Elsevier GmbH. All rights reserved.

Immobilization of swift foxes with ketamine hydrochloride-xylazine hydrochloride

Science.gov (United States)

Telesco, R.L.; Sovada, Marsha A.

2002-01-01

There is an increasing need to develop field immobilization techniques that allow researchers to handle safely swift foxes (Vulpes velox) with minimal risk of stress or injury. We immobilized captive swift foxes to determine the safety and effectiveness of ketamine hydrochloride and xylazine hydrochloride at different dosages. We attempted to determine appropriate dosages to immobilize swift foxes for an adequate field-handling period based on three anesthesia intervals (induction period, immobilization period, and recovery period) and physiologic responses (rectal temperature, respiration rate, and heart rate). Between October 1998–July 1999, we conducted four trials, evaluating three different dosage ratios of ketamine and xylazine (2.27:1.2, 5.68:1.2, and 11.4:1.2 mg/kg ketamine:mg/kg xylazine, respectively), followed by a fourth trial with a higher dosage at the median ratio (11.4 mg/kg ketamine:2.4 mg/kg xylazine). We found little difference in induction and recovery periods among trials 1–3, but immobilization time increased with increasing dosage (Pimmobilization period and recovery period increased in trial 4 compared with trials 1–3 (P≤0.03). There was a high variation in responses of individual foxes across trials, making it difficult to identify an appropriate dosage for field handling. Heart rate and respiration rates were depressed but all physiologic measures remained within normal parameters established for domestic canids. We recommend a dosage ratio of 10 mg/kg ketamine to 1 mg/kg xylazine to immobilize swift foxes for field handling.

Fox Den Disease: An Interesting Case Following Delayed Diagnosis.

Science.gov (United States)

Stehr, Ryan C; Kim, Nicholas; LoGiudice, John A; Ludwig, Kirk

2015-06-01

Pyoderma fistulans sinifica, also known as fox den disease, is a rare and poorly understood inflammatory disorder of the skin and subcutaneous tissues. This disorder is often mistaken for other inflammatory skin disorders and treated inappropriately. The authors describe the case of a 53-year-old male who presented to the colorectal surgery service with a longstanding diagnosis of perirectal Crohn's disease. Despite aggressive immunosuppression and numerous surgical procedures, the patient continued to have unrelenting purulent drainage from the skin of his buttocks. Following wide excision of the affected skin and subcutaneous tissues by the colorectal surgeon, the plastic surgery team reconstructed the 30 cm x 55 cm wound using a combination of local flaps and skin grafts. The initial pathology report of the excised specimen confirmed the presence of nonspecific abscesses and inflammation. Upon special request by the plastic surgery team, the sample was resectioned with the specific intent of establishing a diagnosis of fox den disease. The additional slides met the criteria for an unequivocal diagnosis of fox den disease. Immunosuppression was discontinued and the patient healed his wounds without complication. Fox den disease is often overlooked because of the obscurity of the disease and the special histological sectioning needed to establish a diagnosis. In this case, the patient was unnecessarily treated with immunosuppressive drugs for more than 3 decades because of a misdiagnosis. With increased awareness of fox den disease, perhaps its pathophysiology can be better elucidated as more patients are appropriately diagnosed and treated.

Configuration and stability of 1, 1-diamino-2, 2-dinitrothylene (FOX-7) embedded in graphene

Energy Technology Data Exchange (ETDEWEB)

Wang, Yan Qun [College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou (China); Wang, Gui Xiang [School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing (China)

2016-10-15

The configuration and stability of 1,1-diamino-2,2-dinitroethylene (FOX-7) embedded in graphene were studied using density functional theory with all-electron double numerical polarized basis sets. The results suggested that graphene had a greater impact on the planarity of FOX-7 molecules than did H-bonding. Under the synergistic effect of graphene and H-bonding, the geometry of H-bonded FOX-7 embedded in graphene was flatter than that of FOX-7 without H-bonds, which facilitated π–π stacking, as well as the stability of FOX-7 in graphene. The conjugated structure of FOX-7 contributed to its stability between layers of graphene. When the conjugated structure in FOX-7 was completely disrupted, the stabilization energy decreased by 48.6%. This theoretical work is useful for gaining new insights into the microscopic interaction of energetic molecules with graphene, and it will provide theoretical guidance for the encapsulation and storage of energetic materials.

Configuration and stability of 1, 1-diamino-2, 2-dinitrothylene (FOX-7) embedded in graphene

International Nuclear Information System (INIS)

Wang, Yan Qun; Wang, Gui Xiang

2016-01-01

The configuration and stability of 1,1-diamino-2,2-dinitroethylene (FOX-7) embedded in graphene were studied using density functional theory with all-electron double numerical polarized basis sets. The results suggested that graphene had a greater impact on the planarity of FOX-7 molecules than did H-bonding. Under the synergistic effect of graphene and H-bonding, the geometry of H-bonded FOX-7 embedded in graphene was flatter than that of FOX-7 without H-bonds, which facilitated π–π stacking, as well as the stability of FOX-7 in graphene. The conjugated structure of FOX-7 contributed to its stability between layers of graphene. When the conjugated structure in FOX-7 was completely disrupted, the stabilization energy decreased by 48.6%. This theoretical work is useful for gaining new insights into the microscopic interaction of energetic molecules with graphene, and it will provide theoretical guidance for the encapsulation and storage of energetic materials

High activity antioxidant enzymes protect flying-fox haemoglobin against damage: an evolutionary adaptation for flight?

Science.gov (United States)

Reinke, N B; O'Brien, G M

2006-11-01

Flying-foxes are better able to defend haemoglobin against autoxidation than non-volant mammals such as sheep. When challenged with the common physiological oxidant, hydrogen peroxide, haemolysates of flying-fox red blood cells (RBC) were far less susceptible to methaemoglobin formation than sheep. Challenge with 1-acetyl-2-phenylhydrazine (APH) caused only half as much methaemoglobin formation in flying-fox as in ovine haemolysates. When intact cells were challenged with phenazine methosulfate (PMS), flying-fox RBC partially reversed the oxidant damage, and reduced methaemoglobin from 40 to 20% over 2 h incubation, while ovine methaemoglobin remained at 40%. This reflected flying-fox cells' capacity to replenish GSH fast enough that it did not deplete beyond 50%, while ovine RBC GSH was depleted to around 20%. The greater capacity of flying-foxes to defend haemoglobin against oxidant damage may be explained in part by antioxidant enzymes catalase, superoxide dismutase and cytochrome-b ( 5 ) reductase having two- to four-fold higher activity than in sheep (P foxes.

Resveratrol rescues cadmium-induced mitochondrial injury by enhancing transcriptional regulation of PGC-1α and SOD2 via the Sirt3/FoxO3a pathway in TCMK-1 cells

International Nuclear Information System (INIS)

Fu, Beibei; Zhao, Jiamin; Peng, Wei; Wu, Haibo; Zhang, Yong

2017-01-01

Resveratrol has been reported to ameliorate Cd-induced nephrotoxicity. However, the beneficial effects of resveratrol on Cd-induced nephrotoxicity and the underlying mechanisms of this protection remain unclear. Here, we showed that mouse renal tubular epithelial (TCMK-1) cells exposed to Cd experienced significantly increased mitochondrial reactive oxygen species (mROS) production, as well as decreased mitochondrial biogenesis and function. Cd exposure dramatically decreased Sirt3 protein expression and activity and promoted the acetylation of forkhead box O3 (FoxO3a). Moreover, Cd exposure led to a decreased binding affinity of FoxO3a to the promoters of both peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α and superoxide dismutase 2 (SOD2), powerful and broad regulators of mitochondrial biogenesis and mROS metabolism. Meanwhile, resveratrol remarkably reduced mROS generation by promoting Sirt3 enrichment within the mitochondria and subsequent upregulation of FoxO3a-mediated mitochondria gene expression of PGC-1α and SOD2. Importantly, mechanistic study revealed that ERK1/2 activation was associated with increased apoptosis induced by Cd, resveratrol suppressed Cd-induced apoptosis in mice kidney. Taken together, our data suggest a novel mechanism of action for resveratrol-attenuated Cd-induced cellular damage, which, in part, was mediated through the activation of the Sirt3/FoxO3a signaling pathway. - Highlights: • Resveratrol alleviates Cd-induced mitochondrial damage and improves mitochondrial biogenesis. • Mitochondrial-protective effect of resveratrol on Cd-induced nephrotoxicity is through a Sirt3-FoxO3a-dependent mechanism. • Resveratrol suppresses Cd-induced apoptosis through ERK1/2 in vivo.

bZIPs and WRKYs: two large transcription factor families executing two different functional strategies

Directory of Open Access Journals (Sweden)

Carles eMarco Llorca

2014-04-01

Full Text Available bZIPs and WRKYs are two important plant transcription factor families regulating diverse developmental and stress-related processes. Since a partial overlap in these biological processes is obvious, it can be speculated that they fulfill non-redundant functions in a complex regulatory network. Here, we focus on the regulatory mechanisms that are so far described for bZIPs and WRKYs. bZIP factors need to heterodimerize for DNA-binding and regulation of transcription, and based on a bioinformatics approach, bZIPs can build up more than the double of protein interactions than WRKYs. In contrast, an enrichment of the WRKY DNA-binding motifs can be found in WRKY promoters, a phenomenon which is not observed for the bZIP family. Thus, the two transcription factor families follow two different functional strategies in which WRKYs regulate each other’s transcription in a transcriptional network whereas bZIP action relies on intensive heterodimerization.

Cisplatin- and UV-damaged DNA lure the basal transcription factor TFIID/TBP.

NARCIS (Netherlands)

P. Vichi; F. Coin (Frédéric); J-P. Renaud (Jean-Paul); W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan); D. Moras; J-M. Egly (Jean-Marc)

1997-01-01

textabstractA connection between transcription and DNA repair was demonstrated previously through the characterization of TFIIH. Using filter binding as well as in vitro transcription challenge competition assays, we now show that the promoter recognition factor TATA box-binding protein (TBP)/TFIID

Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo.

Science.gov (United States)

Luo, Wei; Wang, Junxia; Xu, Dengfeng; Bai, Huili; Zhang, Yangli; Zhang, Yuhong; Li, Xiaosong

2018-04-01

In the present study, an artificial zinc-finger transcription factor eukaryotic expression vector specifically recognizing and binding to the hepatitis B virus (HBV) enhancer (Enh) was constructed, which inhibited the replication and expression of HBV DNA. The HBV EnhI‑specific pcDNA3.1‑artificial transcription factor (ATF) vector was successfully constructed, and then transformed or injected into HepG2.2.15 cells and HBV transgenic mice, respectively. The results demonstrated that the HBV EnhI (1,070‑1,234 bp)‑specific ATF significantly inhibited the replication and transcription of HBV DNA in vivo and in vitro. The HBV EnhI‑specific ATF may be a meritorious component of progressive combination therapies for eliminating HBV DNA in infected patients. A radical cure for chronic HBV infection may become feasible by using this bioengineering technology.

Chromosomal mapping of canine-derived BAC clones to the red fox and American mink genomes.

Science.gov (United States)

Kukekova, Anna V; Vorobieva, Nadegda V; Beklemisheva, Violetta R; Johnson, Jennifer L; Temnykh, Svetlana V; Yudkin, Dmitry V; Trut, Lyudmila N; Andre, Catherine; Galibert, Francis; Aguirre, Gustavo D; Acland, Gregory M; Graphodatsky, Alexander S

2009-01-01

High-quality sequencing of the dog (Canis lupus familiaris) genome has enabled enormous progress in genetic mapping of canine phenotypic variation. The red fox (Vulpes vulpes), another canid species, also exhibits a wide range of variation in coat color, morphology, and behavior. Although the fox genome has not yet been sequenced, canine genomic resources have been used to construct a meiotic linkage map of the red fox genome and begin genetic mapping in foxes. However, a more detailed gene-specific comparative map between the dog and fox genomes is required to establish gene order within homologous regions of dog and fox chromosomes and to refine breakpoints between homologous chromosomes of the 2 species. In the current study, we tested whether canine-derived gene-containing bacterial artificial chromosome (BAC) clones can be routinely used to build a gene-specific map of the red fox genome. Forty canine BAC clones were mapped to the red fox genome by fluorescence in situ hybridization (FISH). Each clone was uniquely assigned to a single fox chromosome, and the locations of 38 clones agreed with cytogenetic predictions. These results clearly demonstrate the utility of FISH mapping for construction of a whole-genome gene-specific map of the red fox. The further possibility of using canine BAC clones to map genes in the American mink (Mustela vison) genome was also explored. Much lower success was obtained for this more distantly related farm-bred species, although a few BAC clones were mapped to the predicted chromosomal locations.

MADS interactomics : towards understanding the molecular mechanisms of plant MADS-domain transcription factor function

NARCIS (Netherlands)

Smaczniak, C.D.

2013-01-01

Protein-protein and protein-DNA interactions are essential for the molecular action of transcription factors. By combinatorial binding to target gene promoters, transcription factors are able to up- or down-regulate the expression of these genes. MADS-domain proteins comprise a large family of

Death feigning by ducks in response to predation by red foxes (Vulpes fulva)

Science.gov (United States)

Sargeant, A.B.; Eberhardt, L.E.

1975-01-01

Predation by captive red foxes (Vulpes fulva) on approximately 50 ducks comprised of five species was observed in tests conducted at the Northern Prairie Wildlife Research Center, Jamestown, North Dakota. Most ducks were attacked from a rear or lateral position and seized in the cervical or thoracic region. All birds became immobile (death-feigned) immediately when seized and with few exceptions remained motionless during prey-handling and for varying lengths of time thereafter. Initial death feints lasted from 20 sec to 14 min. Recovery was delayed by tactile, visual and, possibly, auditory cues from the foxes. Death-feigning birds appeared alert and often took advantage of escape opportunities. Twenty-nine birds survived initial capture and handling by the foxes. Naive foxes were wary of ducks during initial confrontations, but experienced foxes showed little hesitation in attacking them. After capture, most ducks were taken alive to lay-down sites where they were mouthed and often killed. Then the ducks were usually cached or taken to dens or pups. Several birds were cached alive. Red foxes appear to have adapted to the escape of death-feigning ducks by learning to kill some birds soon after capture and by the evolution of an appendage-severing behavior. Death feigning appears to be a highly developed antipredator behavior of ducks that facilitates the escape of some birds after capture by red foxes.

NAC Transcription Factors of Barley (Hordeum vulgare L.) and their Involvement in Leaf Senescence

DEFF Research Database (Denmark)

Wagner, Michael

parts of the senescence process. The specific aims of this study were therefore (1) to establish and characterise the NAC transcription factors of the model cereal crop barley (Hordeum vulgare L.) (2) to identify and study putative barley NAC transcription factors involved in the regulation of leaf...

Activity rhythms and distribution of natal dens for red foxes

Science.gov (United States)

Wenyang, Zhou; Wanhong, Wei; Biggins, Dean E.

1995-01-01

The red fox, Vulpes vulpes, was investigated with snow tracking, radiotracking and directive observation at the Haibei Research Station of Alpine Meadow Ecosystem, Academia Sinica, from March to September 1994. The objectives of this study were to determine the distribution and use of natal dens, activity rhythms, and home range sizes for the foxes.

Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin