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Articles 1 - 14 of 14
Full-Text Articles in Entire DC Network
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter
Natalie G. Farny
Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang
Victor R. Ambros
Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously …
The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros
The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros
Victor R. Ambros
Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environmental conditions cause Caenorhabditis elegans larvae to arrest as stress-resistant "dauer" larvae after the second larval stage (L2), thereby indefinitely postponing L3 cell fates. HBL-1 is a key transcriptional regulator of L2 vs. L3 cell fate. Through the analysis of genetic interactions between mutations of hbl-1 and of genes encoding regulators of dauer larva formation, we find that hbl-1 can also modulate the dauer formation decision in a complex manner. We propose that dynamic interactions between …
Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder
Molecular Basis Of Rna Recognition By The Embryonic Polarity Determinant Mex-5, John Pagano, Brian Farley, Lisa Mccoig, Sean Ryder
Sean P. Ryder
Embryonic development requires maternal proteins and RNA. In Caenorhabditis elegans, a gradient of CCCH tandem zinc finger (TZF) proteins coordinates axis polarization and germline differentiation. These proteins govern expression from maternal mRNAs by an unknown mechanism. Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. The minimal binding site is a tract of six or more uridines within a 9-13-nucleotide window. This sequence is remarkably abundant in the 3'-untranslated region of C. elegans transcripts, demonstrating that MEX-5 alone cannot specify mRNA target …
Subnuclear Distribution Of The Vitamin D Receptor, Joseph Bidwell, Andre Van Wijnen, Edward Fey, Harold Merriman, Sheldon Penman, Janet Stein, Gary Stein, Jane Lian
Subnuclear Distribution Of The Vitamin D Receptor, Joseph Bidwell, Andre Van Wijnen, Edward Fey, Harold Merriman, Sheldon Penman, Janet Stein, Gary Stein, Jane Lian
Harold L. Merriman
The subnuclear distribution of the vitamin D receptor was investigated to begin addressing the contribution of nuclear architecture to vitamin D-responsive control of gene expression in ROS 17/2.8 rat osteosarcoma cells. The nuclear matrix is an anastomosing network of filaments that is functionally associated with DNA replication, transcription, and RNA processing. The representation of vitamin D receptor in the nuclear matrix and nonmatrix nuclear fractions was determined by the combined application of 1) sequence-specific interactions with the vitamin D receptor binding element of the rat bone-specific osteocalcin gene promoter and 2) Western blot analysis. Both methods confirmed the presence of …
The Tissue-Specific Nuclear Matrix Protein, Nmp-2, Is A Member Of The Aml/Cbf/Pebp2/Runt Domain Transcription Factor Family: Interactions With The Osteocalcin Gene Promoter, Harold Merriman, Andre Van Wijnen, Scott Hiebert, Joseph Bidwell, Edward Fey, Jane Lian, Janet Stein, Gary Stein
The Tissue-Specific Nuclear Matrix Protein, Nmp-2, Is A Member Of The Aml/Cbf/Pebp2/Runt Domain Transcription Factor Family: Interactions With The Osteocalcin Gene Promoter, Harold Merriman, Andre Van Wijnen, Scott Hiebert, Joseph Bidwell, Edward Fey, Jane Lian, Janet Stein, Gary Stein
Harold L. Merriman
The nuclear matrix protein, NMP-2, was originally identified as an osteoblast-specific DNA-binding complex localized exclusively to the nuclear matrix. NMP-2 was shown to recognize two binding sites, site A (nt-605 to -599) and site B (nt -441 to -435), in the rat bone-specific osteocalcin gene promoter. This study shows that the NMP-2 binding sites A and B as well as a third NMP-2 binding site (nt -135 to -130) constitute a consensus sequence, ATGCTGGT, and represent an AML-1 recognition motif. AML-1 is a member of the AML transcription factor family which is associated with acute myelogenous leukemia and binds to …
Induction Of Bcl-3 By Acute Binge Alcohol Results In Toll-Like Receptor 4/Lps Tolerance, Shashi Bala, Alexander Tang, Donna Catalano, Jan Petrasek, Odette Taha, Karen Kodys, Gyongyi Szabo
Induction Of Bcl-3 By Acute Binge Alcohol Results In Toll-Like Receptor 4/Lps Tolerance, Shashi Bala, Alexander Tang, Donna Catalano, Jan Petrasek, Odette Taha, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Acute alcohol binge results in immunosuppression and impaired production of proinflammatory cytokines, including TNF-alpha. TNF-alpha production is induced by LPS, a TLR4 ligand, and is tightly regulated at various levels of the signaling cascade, including the NF-kappaB transcription factor. Here, we hypothesized that acute alcohol induces TLR4/LPS tolerance via Bcl-3, a nuclear protein and member of the NF-kappaB family. We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on TLR4-induced TNF-alpha production in human monocytes and murine RAW 264.7 macrophages. Acute alcohol-induced Bcl-3 expression and IP studies revealed increased association of Bcl-3 with NF-kappaB …
Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc
Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc
Gyongyi Szabo
BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …
Signalling Pathways In Alcohol-Induced Liver Inflammation, Pranoti Mandrekar, Gyongyi Szabo
Signalling Pathways In Alcohol-Induced Liver Inflammation, Pranoti Mandrekar, Gyongyi Szabo
Gyongyi Szabo
The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFkappaB, AP-1 leads to increased inflammatory cytokine production in …
Nf-Kb, A Prototypical Cytokine-Regulated Transcription Factor: Implications For Alcohol-Mediated Responses, Samir Zakhari, Gyongyi Szabo
Nf-Kb, A Prototypical Cytokine-Regulated Transcription Factor: Implications For Alcohol-Mediated Responses, Samir Zakhari, Gyongyi Szabo
Gyongyi Szabo
Summary of the presentations and discussions held at the symposium NF-KB, a Prototypical Cytokine-Regulated Transcription Factor: Implications for Alcohol-Mediated Responses, held during the Joint RSMSBRA meeting in Washington, D.C. in June 1996.
Diverse Regulation Of Nf-Kappab And Peroxisome Proliferator-Activated Receptors In Murine Nonalcoholic Fatty Liver, Laszlo Romics, Karen Kodys, Angela Dolganiuc, Lucia Graham, Arumugam Velayudham, Pranoti Mandrekar, Gyongyi Szabo
Diverse Regulation Of Nf-Kappab And Peroxisome Proliferator-Activated Receptors In Murine Nonalcoholic Fatty Liver, Laszlo Romics, Karen Kodys, Angela Dolganiuc, Lucia Graham, Arumugam Velayudham, Pranoti Mandrekar, Gyongyi Szabo
Gyongyi Szabo
Fatty liver is highly sensitive to inflammatory activation. Peroxisome proliferator-activated receptors (PPAR) have anti-inflammatory effects and regulate lipid metabolism in the fatty liver. We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro- and anti-inflammatory signals. Leptin-deficient, ob/ob mice and their lean littermates were challenged with single or double insults and pro- and anti-inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF-kappaB and peroxisome proliferator receptor element (PPRE). Ob/ob mice produced significantly higher serum tumor necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 and showed increased hepatic NF-kappaB activation compared to …
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Gyongyi Szabo
The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …
The Lin-41 Rbcc Gene Acts In The C. Elegans Heterochronic Pathway Between The Let-7 Regulatory Rna And The Lin-29 Transcription Factor, Frank Slack, Michael Basson, Zhongchi Liu, Victor Ambros, H. Horvitz, Gary Ruvkun
The Lin-41 Rbcc Gene Acts In The C. Elegans Heterochronic Pathway Between The Let-7 Regulatory Rna And The Lin-29 Transcription Factor, Frank Slack, Michael Basson, Zhongchi Liu, Victor Ambros, H. Horvitz, Gary Ruvkun
Victor R. Ambros
Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval fates. let-7 mutations cause similar reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression. lin-41 encodes an RBCC protein, and two elements in the lin-413'UTR are complementary to the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is downregulated in the tissues affected by lin-41 at the time that the let-7 …
The Heterochronic Gene Lin-29 Encodes A Zinc Finger Protein That Controls A Terminal Differentiation Event In Caenorhabditis Elegans, Ann Rougvie, Victor Ambros
The Heterochronic Gene Lin-29 Encodes A Zinc Finger Protein That Controls A Terminal Differentiation Event In Caenorhabditis Elegans, Ann Rougvie, Victor Ambros
Victor R. Ambros
A hierarchy of heterochronic genes, lin-4, lin-14, lin-28 and lin-29, temporally restricts terminal differentiation of Caenorhabditis elegans hypodermal seam cells to the final molt. This terminal differentiation event involves cell cycle exit, cell fusion and the differential regulation of genes expressed in the larval versus adult hypodermis. lin-29 is the most downstream gene in the developmental timing pathway and thus it is the most direct known regulator of these diverse processes. We show that lin-29 encodes a protein with five zinc fingers of the (Cys)2-(His)2 class and thus likely controls these processes by regulating transcription in a stage-specific manner. Consistent …