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Chicago Ridge, IL, United States

Srivastava L.,Rutgers University | Srivastava L.,University of Georgia | Lapik Y.R.,University of Illinois at Chicago | Lapik Y.R.,Harold Washington College | And 2 more authors.
Molecular and Cellular Biology | Year: 2010

Biogenesis of eukaryotic ribosomes requires a number of RNA helicases that drive molecular rearrangements at various points of the assembly pathway. While many ribosome synthesis factors are conserved among all eukaryotes, certain features of ribosome maturation, such as U8 snoRNA-assisted processing of the 5.8S and 28S rRNA precursors, are observed only in metazoan cells. Here, we identify the mammalian DEAD box helicase family member Ddx51 as a novel ribosome synthesis factor and an interacting partner of the nucleolar GTP-binding protein Nog1. Unlike any previously studied yeast helicases, Ddx51 is required for the formation of the 3′ end of 28S rRNA. Ddx51 binds to pre-60S subunit complexes and promotes displacement of U8 snoRNA from pre-rRNA, which is necessary for the removal of the 3′ external transcribed spacer from 28S rRNA and productive downstream processing. These data demonstrate the emergence of a novel factor that facilitates a pre-rRNA processing event specific for higher eukaryotes. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Huber P.,University of Illinois at Chicago | Crum T.,University of Illinois at Chicago | Crum T.,Benedictine University | Clary L.M.,University of Illinois at Chicago | And 5 more authors.
Cellular and Molecular Life Sciences | Year: 2013

T-box transcription factors are critical developmental regulators in all multi-cellular organisms, and altered T-box factor activity is associated with a variety of human congenital diseases and cancers. Despite the biological significance of T-box factors, their mechanism of action is not well understood. Here we examine whether SUMOylation affects the function of the C. elegans Tbx2 sub-family T-box factor TBX-2. We have previously shown that TBX-2 interacts with the E2 SUMO-conjugating enzyme UBC-9, and that loss of TBX-2 or UBC-9 produces identical defects in ABa-derived pharyngeal muscle development. We now show that TBX-2 is SUMOylated in mammalian cell assays, and that both UBC-9 interaction and SUMOylation depends on two SUMO consensus sites located in the T-box DNA binding domain and near the TBX-2 C-terminus, respectively. In co-transfection assays, a TBX-2:GAL4 fusion protein represses expression of a 5xGal4:tk:luciferase construct. However, this activity does not require SUMOylation, indicating SUMO is not generally required for TBX-2 repressor activity. In C. elegans, reducing SUMOylation enhances the phenotype of a temperature-sensitive tbx-2 mutant and results in ectopic expression of a gene normally repressed by TBX-2, demonstrating that SUMOylation is important for TBX-2 function in vivo. Finally, we show mammalian orthologs of TBX-2, Tbx2, and Tbx3, can also be SUMOylated, suggesting SUMOylation may be a conserved mechanism controlling T-box factor activity. © 2013 The Author(s).

Milton A.C.,University of Illinois at Chicago | Packard A.V.,University of Illinois at Chicago | Clary L.,University of Illinois at Chicago | Clary L.,Harold Washington College | Okkema P.G.,University of Illinois at Chicago
Developmental Biology | Year: 2013

T-box genes are frequently expressed in dynamic patterns during animal development, but the mechanisms controlling expression of these genes are not well understood. The Caenorhabditis elegans T-box gene tbx-2 is essential for development of the ABa-derived pharyngeal muscles, specification of neural cell fate in the HSN/PHB lineage, and adaptation in olfactory neurons. The tbx-2 expression pattern is complex, and expression has been described in pharyngeal precursors and body wall muscles during embryogenesis, and amphid sensory neurons and pharyngeal neurons in adults. To examine mechanisms regulating tbx-2 gene expression, we performed an RNAi screen of transcription factor genes in strains containing a Ptbx-2::gfp reporter and identified the Nuclear Factor Y (NF-Y) complex as a negative regulator of tbx-2 expression. NF-Y is a heterotrimeric CCAAT-binding complex consisting of A-C subunits, and reduction of the NF-Y subunits nfya-1, nfyb-1, or nfyc-1 by RNAi or using mutants results in ectopic Ptbx-2::gfp expression in hypodermal seam cells and gut. Mutation of two CCAAT-boxes in the tbx-2 promoter results in a similar pattern of ectopic Ptbx-2::gfp expression, suggesting NF-Y directly represses the tbx-2 promoter. tbx-2 mRNA is moderately increased in nfya-1 null mutants, indicating NF-Y represses expression of endogenous tbx-2. Finally we identify and characterize a second-site mutation that enhances lethality of a temperature sensitive tbx-2 mutant and show that this mutation is a deletion in the nfyb-1 gene. Together, these results identify NF-Y as an important regulator of tbx-2 function in vivo. © 2013 Elsevier Inc.

McMorris F.R.,Illinois Institute of Technology | McMorris F.R.,University of Louisville | Mulder H.M.,Erasmus University Rotterdam | Ortega O.,Harold Washington College
Networks | Year: 2012

A p-value of a sequence π = (x 1, x 2,⋯, x k) of elements of a finite metric space (X, d) is an element x for which ∑ i=1 k dp(x,xi) is minimum. The function ℓ p with domain the set of all finite sequences defined by ℓ p(π) = {x: x is a p-value of π} is called the ℓ p-function on X. The ℓ p-functions with p = 1 and p = 2 are the well-studied median and mean functions respectively. In this article, the ℓ p-function on finite trees is characterized axiomatically. © 2011 Wiley Periodicals, Inc.

Chawla R.,Phoenix Childrens Hospital | Alden T.D.,Northwestern University | Bizhanova A.,Harold Washington College | Kadakia R.,Northwestern University | And 2 more authors.
Thyroid | Year: 2015

Background: Congenital hyperthyroidism can be a cause of failure to thrive, hyperactivity, developmental delay, and craniosynostosis during infancy. Most commonly, the condition occurs in the setting of maternal autoimmune thyroid disease. Rarely, congenital hyperthyroidism can also occur secondary to activating mutations within the thyrotropin (TSH) receptor. Patient Findings: A Hispanic male infant presented at age 6 months with severe thyrotoxicosis. At the time of presentation he was being evaluated for squamosal suture synostosis and he was noted to have significant developmental delays. Summary: The patient's thyrotoxicosis was initially treated with antithyroid medication, and he subsequently underwent craniosynostosis repair leading to neurodevelopmental improvement. DNA from the patient and his parents was submitted for mutational analysis of exons 9 and 10 of the TSH receptor. He was found to carry a monoallelic transition 1895C>T in exon 10 that resulted in the substitution of threonine at position 632 by isoleucine (T32I). This mutation resulted in constitutive activation of the TSH receptor. Neither parent carried this mutation indicating that the child has acquired a de novo germline mutation. Conclusions: We report the first case of squamosal suture craniosynostosis in a patient with non-autoimmune hyperthyroidism. Squamosal suture craniosynotosis is rare, often has a subtle presentation, and should be considered in all patients with this condition because prompt treatment of hyperthyroidism and craniosynotosis repair can lead to normalization of neurodevelopment. © Mary Ann Liebert, Inc. 2015.

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