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Search Results: 1 - 10 of 169279 matches for " Fred E. Indig "
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The Nucleolus Takes Control of Protein Trafficking Under Cellular Stress
Narasimharao Nalabothula,Fred E Indig,France Carrier
Molecular and Cellular Pharmacology , 2010,
Abstract: The nucleolus is a highly dynamic nuclear substructure that was originally described as the site of ribosome biogenesis. The advent of proteomic analysis has now allowed the identification of over 4500 nucleolus associated proteins with only about 30% of them associated with ribogenesis (1). The great number of nucleolar proteins not associated with traditionally accepted nucleolar functions indicates a role for the nucleolus in other cellular functions such as mitosis, cell-cycle progression, cell proliferation and many forms of stress response including DNA repair (2). A number of recent reviews have addressed the pivotal role of the nucleolus in the cellular stress response (1, 3, 4). Here, we will focus on the role of Nucleolin and Nucleophosmin, two major components of the nucleolus, in response to genotoxic stress. Due to space constraint only a limited number of studies are cited. We thus apologize to all our colleagues whose works are not referenced here.
Nucleolin Binds to the Proliferating Cell Nuclear Antigen and Inhibits Nucleotide Excision Repair
Chonglin Yang,Myoung Sook Kim,Devulapalli Chakravarty,Fred E. Indig
Molecular and Cellular Pharmacology , 2009,
Abstract: Nucleolin is over-expressed in malignant tumors and is used as a marker for cell proliferation and to reliably predict tumor growth rate. However, it is not known whether nucleolin expression is directly involved in or is a consequence of carcinogenesis. Using GST-pull down assays, we have determined that the recombinant nucleolin interacts with the Proliferating Cell Nuclear Antigen (PCNA). Co-immunoprecipitation assays indicate that the nucleolin-PCNA interaction also occurs in intact cells and this interaction increases after exposure of colon carcinoma RKO cells to UV radiation. Moreover, our data indicate that PCNA and nucleolin co-localize in some areas within the RKO cell nuclei. The functional significance of this interaction is evaluated on Nucleotide Excision Repair (NER) since PCNA is a primary mediator of this cellular function. Our data indicate that overexpression of nucleolin decreases the repair efficiency of UV damaged plasmid DNA in RKO cells. Co-transfection with PCNA can rescue this effect in vivo. Furthermore, reduction of nucleolin protein levels increases DNA repair efficiency in RKO and CHO cells and consequently increases cell survival. These data indicate that the direct interaction of nucleolin with PCNA inhibits NER efficiency of UV damaged DNA. This effect could contribute to carcinogenesis and aging in cells over-expressing nucleolin.
Nucleolin Inhibits G4 Oligonucleotide Unwinding by Werner Helicase
Fred E. Indig, Ivana Rybanska, Parimal Karmakar, Chakravarty Devulapalli, Haiqing Fu, France Carrier, Vilhelm A. Bohr
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035229
Abstract: Background The Werner protein (WRNp), a member of the RecQ helicase family, is strongly associated with the nucleolus, as is nucleolin (NCL), an important nucleolar constituent protein. Both WRNp and NCL respond to the effects of DNA damaging agents. Therefore, we have investigated if these nuclear proteins interact and if this interaction has a possible functional significance in DNA damage repair. Methodology/Principal Findings Here we report that WRNp interacts with the RNA-binding protein, NCL, based on immunoprecipitation, immunofluorescent co-localization in live and fixed cells, and direct binding of purified WRNp to nucleolin. We also map the binding region to the C-terminal domains of both proteins. Furthermore, treatment of U2OS cells with 15 μM of the Topoisomerase I inhibitor, camptothecin, causes the dissociation of the nucleolin-Werner complex in the nucleolus, followed by partial re-association in the nucleoplasm. Other DNA damaging agents, such as hydroxyurea, Mitomycin C, and aphidicolin do not have these effects. Nucleolin or its C-terminal fragment affected the helicase, but not the exonuclease activity of WRNp, by inhibiting WRN unwinding of G4 tetraplex DNA structures, as seen in activity assays and electrophoretic mobility shift assays (EMSA). Conclusions/Significance These data suggest that nucleolin may regulate G4 DNA unwinding by WRNp, possibly in response to certain DNA damaging agents. We postulate that the NCL-WRNp complex may contain an inactive form of WRNp, which is released from the nucleolus upon DNA damage. Then, when required, WRNp is released from inhibition and can participate in the DNA repair processes.
PKC and PKA Phosphorylation Affect the Subcellular Localization of Claudin-1 in Melanoma Cells
Amanda D. French, Jennifer L. Fiori, Tura C. Camilli, Poloko D. Leotlela, Michael P. O'Connell, Brittany P. Frank, Sarah Subaran, Fred. E. Indig, Dennis D. Taub, Ashani T. Weeraratna
International Journal of Medical Sciences , 2009,
Abstract: Cytoplasmic expression of claudin-1 in metastatic melanoma cells correlates to increased migration, and increased secretion of MMP-2 in a PKC dependent manner, whereas claudin-1 nuclear expression is found in benign nevi. Melanoma cells were transfected with a vector expressing CLDN-1 fused to a nuclear localization signal (NLS). Despite significant nuclear localization of claudin-1, there was still transport of claudin-1 to the cytoplasm. Phorbol ester treatment of cells transfected with NLS-claudin-1 resulted in an exclusion of claudin-1 from the nucleus, despite the NLS. To ascertain whether PKC or PKA were involved in this translocation, we mutated the putative phosphorylation sites within the protein. We found that mutating the PKC phosphorylation sites to mimic a non-phosphorylated state did not cause a shift of claudin-1 to the nucleus of the cells, but mutating the PKA sites did. Mutations of either site to mimic constitutive phosphorylation resulted in cytoplasmic claudin-1 expression. Stable claudin-1 transfectants containing non-phosphorylatable PKA sites exhibited decreased motility. These data imply that subcellular localization of claudin-1 can be controlled by phosphorylation, dicating effects on metastatic capacity.
Workplace violence in a large correctional health service in New South Wales, Australia: a retrospective review of incident management records
Cashmore Aaron W,Indig Devon,Hampton Stephen E,Hegney Desley G
BMC Health Services Research , 2012, DOI: 10.1186/1472-6963-12-245
Abstract: Background Little is known about workplace violence among correctional health professionals. This study aimed to describe the patterns, severity and outcomes of incidents of workplace violence among employees of a large correctional health service, and to explore the help-seeking behaviours of staff following an incident. Methods The study setting was Justice Health, a statutory health corporation established to provide health care to people who come into contact with the criminal justice system in New South Wales, Australia. We reviewed incident management records describing workplace violence among Justice Health staff. The three-year study period was 1/7/2007-30/6/2010. Results During the period under review, 208 incidents of workplace violence were recorded. Verbal abuse (71%) was more common than physical abuse (29%). The most (44%) incidents of workplace violence (including both verbal and physical abuse) occurred in adult male prisons, although the most (50%) incidents of physical abuse occurred in a forensic hospital. Most (90%) of the victims were nurses and two-thirds were females. Younger employees and males were most likely to be a victim of physical abuse. Preparing or dispensing medication and attempting to calm and/or restrain an aggressive patient were identified as ‘high risk’ work duties for verbal abuse and physical abuse, respectively. Most (93%) of the incidents of workplace violence were initiated by a prisoner/patient. Almost all of the incidents received either a medium (46%) or low (52%) Severity Assessment Code. Few victims of workplace violence incurred a serious physical injury – there were no workplace deaths during the study period. However, mental stress was common, especially among the victims of verbal abuse (85%). Few (6%) victims of verbal abuse sought help from a health professional. Conclusions Among employees of a large correctional health service, verbal abuse in the workplace was substantially more common than physical abuse. The most incidents of workplace violence occurred in adult male prisons. Review of the types of adverse health outcomes experienced by the victims of workplace violence and the assessments of severity assigned to violent incidents suggests that, compared with health care settings in the community, correctional settings are fairly safe places in which to practice.
Involvement of mTOR in CXCL12 Mediated T Cell Signaling and Migration
Rachel Munk, Paritosh Ghosh, Manik C. Ghosh, Takeshi Saito, Mai Xu, Arnell Carter, Fred Indig, Dennis D. Taub, Dan L. Longo
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024667
Abstract: Background CXCL12 is a pleiotropic chemokine involved in multiple different processes such as immune regulation, inflammatory responses, and cancer development. CXCL12 is also a potent chemokine involved in chemoattraction of T cells to the site of infection or inflammation. Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that modulates different cellular processes, such as metabolism, nutrient sensing, protein translation, and cell growth. The role of mTOR in CXCL12-mediated resting T cell migration has yet to be elucidated. Methodology/Principal Findings Rapamycin, an inhibitor of mTOR, significantly inhibits CXCL12 mediated migration of both primary human resting T cells and human T cell leukemia cell line CEM. p70S6K1, an effector molecule of mTOR signaling pathway, was knocked down by shRNA in CEM cells using a lentiviral gene transfer system. Using p70S6K1 knock down cells, we demonstrate the role of mTOR signaling in T cell migration both in vitro and in vivo. Conclusions Our data demonstrate a new role for mTOR in CXCL12-induced T cell migration, and enrich the current knowledge regarding the clinical use of rapamycin.
Joutes de freestyle - faut-il rimer ou bien se moquer?
Teperman, Ricardo Indig;
Vibrant: Virtual Brazilian Anthropology , 2011, DOI: 10.1590/S1809-43412011000100002
Abstract: in this article i discuss the practice of rhyme improvisation duel in rap, known as freestyle battles, in which, according to the early practitioners, the goal is to “mock the opponent”. based on a research carried out for two years at the battle of santa cruz, in s?o paulo, i analyse how the musical and performance aspects contribute to “alleviate the bitterness” caused by the deride. while analysing the contents of the improvising speech, i propose to consider the mobilized categories - such as gender, age, race/color, class - operating as differential signs that yield a significance exclusively by means of the articulations achieved during each battle, and have no sense if viewed isolatedly.
Fred Bateman,Jason E. Taylor
Essays in Economic & Business History , 2008,
Abstract: For more than three decades, scholars have examined the grossly unequal state- level per capita distribution of New Deal spending. Why did small population rural states such as Nevada, Montana, and Wyoming receive up to six times as many federal dollars per capita as densely populated states such as Connecticut, Rhode Island, and New York? Empirical studies employing economic and political variables have had mixed results in explaining this distribution. What past studies neglect is that a large proportion of New Deal dollars went towards the creation ofpublic goods, which had spillover effects particularly upon those who lived in close proximity to these projects. This paper suggests that the state-level distribution of per capita expenditures during the 1930s is consistent with what would be expected to follow from an economically efficient allocation ofpublic goods.
Fred Bateman,Jason E. Taylor
Essays in Economic & Business History , 2002,
Abstract: Franklin Roosevelt publicly stated his devotion to the American South and pledged to help reform the region’s laggard economy. However, Southern states received significantly fewer federal expenditures per capita, both during the New Deal of the 1930s and the military emergency of the 1940s. This article investigates economic, political, and strategic reasons for this result. Additionally, we apply a public goods perspective to New Deal and World War II spending and propose that lower levels of per capita spending in the South do not necessarily translate into a smaller impact of that spending.
Metallicity and Far-Infrared Luminosity of High Redshift Quasars
Leah E. Simon,Fred Hamann
Physics , 2010, DOI: 10.1111/j.1365-2966.2010.17022.x
Abstract: We present the results of an exploratory study of broad line region (BLR) metallicity in 34 2.2 < z < 4.6 quasars with far-infrared (FIR) luminosities (L_FIR) from 10^13.4 to 10^12.1 L_\odot . Quasar samples sorted by L_FIR might represent an evolutionary sequence if the star formation rates (SFRs) in quasar hosts generally diminish across quasar lifetimes. We use rest-frame ultraviolet spectra from the Sloan Digital Sky Survey to construct three composite spectra sorted by L_FIR, corresponding to average SFRs of 4980, 2130 and 340 M_\odot yr^-1 after correcting for a nominal quasar FIR contribution. The measured N V {\lambda} 1240/C IV {\lambda} 1550 and Si IV {\lambda} 1397+O IV] {\lambda} 1402/C IV {\lambda} 1550 emission line ratios indicate super-solar BLR metallicities in all three composites, with no evidence for a trend with the star formation rate. The formal derived metallicities, Z ~ 5-9 Z_\odot , are similar to those derived for the BLRs of other quasars at similar redshifts and luminosities. These results suggest that the ongoing star formation in the host is not responsible for the metal enrichment of the BLR gas. Instead, the BLR gas must have been enriched before the visible quasar phase. These results for high quasar metallicities, regardless of L_FIR, are consistent with evolution scenarios wherein visibly bright quasars appear after the main episode(s) of star formation and metal enrichment in the host galaxies. Finally, young quasars, those more closely associated with a recent merger or a blowout of gas and dust, may exhibit tracers of these events, such as redder continuum slopes and higher incidence of narrow absorption lines. With the caveat of small sample sizes, we find no relation between L_FIR and the reddening or the incidence of absorption lines.
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