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  • 1
    Publication Date: 2014-02-28
    Description: The use of multiple replication origins in archaea is not well understood. In particular, little is known about their specific control mechanisms. Here, we investigated the active replication origins in the three replicons of a halophilic archaeon, Haloarcula hispanica , by extensive gene deletion, DNA mutation and genome-wide marker frequency analyses. We revealed that individual origins are specifically dependent on their co-located cdc6 genes, and a single active origin/ cdc6 pairing is essential and sufficient for each replicon. Notably, we demonstrated that the activities of oriC1 and oriC2 , the two origins on the main chromosome, are differently controlled. A G-rich inverted repeat located in the internal region between the two inverted origin recognition boxes (ORBs) plays as an enhancer for oriC1 , whereas the replication initiation at oriC2 is negatively regulated by an ORB-rich region located downstream of oriC2-cdc6E , likely via Cdc6E-titrating. The oriC2 placed on a plasmid is incompatible with the wild-type (but not the oriC2 ) host strain, further indicating that strict control of the oriC2 activity is important for the cell. This is the first report revealing diverse control mechanisms of origins in haloarchaea, which has provided novel insights into the use and coordination of multiple replication origins in the domain of Archaea.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2014-09-23
    Description: The Gangdese magmatic arc, southeastern Tibet, was built by mantle-derived magma accretion and juvenile crustal growth during the Mesozoic to Early Cenozoic northward subduction of the Neo-Tethyan oceanic slab beneath the Eurasian continent. The petrological and geochronological data reveal that the lower crust of the southeastern Gangdese arc experienced Oligocene reworking by metamorphism, anatexis and magmatism after the India and Asia collision. The post-collisional metamorphic and migmatitic rocks formed at 34–26 Ma and 28–26 Ma, respectively. Meta-granitoids have protolith ages of 65–38 Ma. Inherited detrital zircon from metasedimentary rocks has highly variable ages ranging from 2708 to 37 Ma. These rocks underwent post-collisional amphibolite-facies metamorphism and coeval anatexis under P–T conditions of ~710–760 °C and ~12 kbar with geothermal gradients of 18–20 °C km − 1 , indicating a distinct crustal thickening process. Crustal shortening, thickening and possible subduction erosion due to the continental collision and ongoing convergence resulted in high-pressure metamorphic and anatectic reworking of the magmatic and sedimentary rocks of the deep Gangdese arc. This study provides a typical example of the reworking of juvenile and ancient continental crust during active collisional orogeny. This article is protected by copyright. All rights reserved.
    Print ISSN: 0263-4929
    Electronic ISSN: 1525-1314
    Topics: Geosciences
    Published by Wiley
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  • 3
    Publication Date: 2014-11-07
    Description: Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis Cell Death and Disease 5, e1516 (November 2014). doi:10.1038/cddis.2014.493 Authors: T Liu, R J Kishton, A N Macintyre, V A Gerriets, H Xiang, X Liu, E D Abel, D Rizzieri, J W Locasale & J C Rathmell
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 4
    Publication Date: 2012-05-02
    Description: HA22 is a recombinant immunotoxin composed of an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A. HA22 produced a high rate of complete remissions in drug-resistant hairy cell leukemia and has a lower response rate in pediatric acute lymphoblastic leukemia (ALL). To understand why patients with ALL have poorer responses, we isolated an ALL cell line that is resistant to killing by HA22. The resistance is unstable; without HA22 the cells revert to HA22 sensitivity in 4 mo. We showed that in the resistant cell line, HA22 is unable to ADP ribosylate and inactivate elongation factor-2 (EF2), owing to a low level of DPH4 mRNA and protein, which prevents diphthamide biosynthesis and renders EF2 refractory to HA22. Analysis of the promoter region of the DPH4 gene shows that the CpG island was hypomethylated in the HA22-sensitive cells, heavily methylated in the resistant cells, and reverted to low methylation in the revertant cells. Our data show that immunotoxin resistance is associated with reversible CpG island methylation and silencing of DPH4 gene transcription. Incubation of sensitive cells with the methylation inhibitor 5-azacytidine prevented the emergence of resistant cells, suggesting that this agent in combination with HA22 may be useful in the treatment of some cases of ALL.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2011-11-24
    Description: In this paper we are interested in finding approximate solutions to a Volterra integral equation of the first kind with a highly oscillatory Bessel kernel. We begin our analysis by showing the relationship between the integral of a highly oscillatory Bessel function and the order of the integrand Bessel function. We then establish the asymptotic expansion of the exact solution of the Volterra integral equation in inverse powers of the frequency and develop a Filon-type method to provide approximations. Numerical examples are provided to demonstrate the effectiveness of the proposed method.
    Print ISSN: 0272-4979
    Electronic ISSN: 1464-3642
    Topics: Mathematics
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  • 6
    Publication Date: 2015-04-04
    Description: Heparanase (HPSE) is the endogenous endoglycosidase that degrades heparan sulfate proteoglycans and promotes the tumor growth, invasion, metastasis and angiogenesis. Our previous studies have shown that HPSE is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. However, the underlying regulatory mechanisms remain largely unknown. In this study, we identified one binding site of microRNA-558 (miR-558) within the HPSE promoter. In NB tissues and cell lines, miR-558 was up-regulated and positively correlated with HPSE expression. Gain- and loss-of-function studies demonstrated that miR-558 facilitated the transcript and protein levels of HPSE and its downstream gene, vascular endothelial growth factor, in NB cell lines. In addition, miR-558 enhanced the promoter activities of HPSE , and these effects were abolished by the mutation of the miR-558-binding site. Mechanistically, miR-558 induced the enrichment of the active epigenetic marker and RNA polymerase II on the HPSE promoter in NB cells in an Argonaute 1-dependent manner, which was abolished by repressing the miR-558-promoter interaction. Knockdown of endogenous miR-558 decreased the growth, invasion, metastasis and angiogenesis of NB cells in vitro and in vivo . In contrast, over-expression of miR-558 promoted the growth, invasion, metastasis and angiogenesis of SH-SY5Y and SK-N-SH cells. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by knockdown or over-expression of miR-558. These data indicate that miR-558 induces the transcriptional activation of HPSE via the binding site within promoter, thus facilitating the tumorigenesis and aggressiveness of NB.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2014-10-17
    Description: Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis Cell Death and Disease 5, e1470 (October 2014). doi:10.1038/cddis.2014.431 Authors: T Liu, R J Kishton, A N Macintyre, V A Gerriets, H Xiang, X Liu, E Dale Abel, D Rizzieri, J W Locasale & J C Rathmell
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 8
    Publication Date: 2012-02-01
    Description: In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2018-09-14
    Description: The Ugi reaction constructs α-acylaminoamide compounds by combining an aldehyde or ketone, an amine, a carboxylic acid, and an isocyanide in a single flask. Its appealing features include inherent atom and step economy together with the potential to generate products of broad structural diversity. However, control of the stereochemistry in this reaction has proven to be a formidable challenge. We describe an efficient enantioselective four-component Ugi reaction catalyzed by a chiral phosphoric acid derivative that delivers more than 80 α-acylaminoamides in good to excellent enantiomeric excess. Experimental and computational studies establish the reaction mechanism and origins of stereoselectivity.
    Keywords: Chemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2007-09-29
    Description: The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278242/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Chih-Chin -- Lam, Son N -- Acharya, Priyamvada -- Tang, Min -- Xiang, Shi-Hua -- Hussan, Syed Shahzad-Ul -- Stanfield, Robyn L -- Robinson, James -- Sodroski, Joseph -- Wilson, Ian A -- Wyatt, Richard -- Bewley, Carole A -- Kwong, Peter D -- P30 AI060354/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-03/AI/NIAID NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 28;317(5846):1930-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17901336" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD4/*chemistry/immunology ; Crystallography, X-Ray ; HIV Antibodies/*chemistry/immunology ; HIV Envelope Protein gp120/*chemistry/immunology/metabolism ; HIV-1/metabolism ; Humans ; Models, Molecular ; Molecular Mimicry ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Peptide Fragments/chemistry/metabolism ; Receptors, CCR5/*chemistry/metabolism ; Sulfates/metabolism ; Tyrosine/metabolism ; Virus Internalization
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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