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Search Results: 1 - 10 of 199111 matches for " Glen N. Barber "
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Impaired Cellular Responses to Cytosolic DNA or Infection with Listeria monocytogenes and Vaccinia Virus in the Absence of the Murine LGP2 Protein
Darja Pollpeter,Akihiko Komuro,Glen N. Barber,Curt M. Horvath
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018842
Abstract: Innate immune signaling is crucial for detection of and the initial response to microbial pathogens. Evidence is provided indicating that LGP2, a DEXH box domain protein related to the RNA recognition receptors RIG-I and MDA5, participates in the cellular response to cytosolic double-stranded DNA (dsDNA). Analysis of embryonic fibroblasts and macrophages from mice harboring targeted disruption in the LGP2 gene reveals that LGP2 can act as a positive regulator of type I IFN and anti-microbial gene expression in response to transfected dsDNA. Results indicate that infection of LGP2-deficient mice with an intracellular bacterial pathogen, Listeria monocytogenes, leads to reduced levels of type I IFN and IL12, and allows increased bacterial growth in infected animals, resulting in greater colonization of both spleen and liver. Responses to infection with vaccinia virus, a dsDNA virus, are also suppressed in cells lacking LGP2, reinforcing the ability of LGP2 to act as a positive regulator of antiviral signaling. In vitro mechanistic studies indicate that purified LGP2 protein does not bind DNA but instead mediates these responses indirectly. Data suggest that LGP2 may be acting downstream of the intracellular RNA polymerase III pathway to activate anti-microbial signaling. Together, these findings demonstrate a regulatory role for LGP2 in the response to cytosolic DNA, an intracellular bacterial pathogen, and a DNA virus, and provide a plausible mechanistic hypothesis as the basis for this activity.
DDX24 Negatively Regulates Cytosolic RNA-Mediated Innate Immune Signaling
Zhe Ma,Robert Moore,Xiangxi Xu,Glen N. Barber
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003721
Abstract: RIG-I-Like Receptors (RLRs) sense cytosolic viral RNA to transiently activate type I IFN production. Here, we report that a type I IFN inducible DExD/H helicase, DDX24, exerts a negative-regulatory effect on RLR function. Expression of DDX24 specifically suppressed RLR activity, while DDX24 loss, which caused embryonic lethality, augmented cytosolic RNA-mediated innate signaling and facilitated RNA virus replication. DDX24 preferentially bound to RNA rather than DNA species and influenced signaling by associating with adaptor proteins FADD and RIP1. These events preferentially impeded IRF7 activity, an essential transcription factor for type I IFN production. Our data provide a new function for DDX24 and help explain innate immune gene regulation, mechanisms that may additionally provide insight into the causes of inflammatory disease.
TBK1 Protects Vacuolar Integrity during Intracellular Bacterial Infection
Andrea L Radtke,Laura M Delbridge,Siddharth Balachandran,Glen N Barber,Mary X. D O'Riordan
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030029
Abstract: TANK-binding kinase-1 (TBK1) is an integral component of Type I interferon induction by microbial infection. The importance of TBK1 and Type I interferon in antiviral immunity is well established, but the function of TBK1 in bacterial infection is unclear. Upon infection of murine embryonic fibroblasts with Salmonella enterica serovar Typhimurium (Salmonella), more extensive bacterial proliferation was observed in tbk1?/? than tbk1+/+ cells. TBK1 kinase activity was required for restriction of bacterial infection, but interferon regulatory factor-3 or Type I interferon did not contribute to this TBK1-dependent function. In tbk1?/?cells, Salmonella, enteropathogenic Escherichia coli, and Streptococcus pyogenes escaped from vacuoles into the cytosol where increased replication occurred, which suggests that TBK1 regulates the integrity of pathogen-containing vacuoles. Knockdown of tbk1 in macrophages and epithelial cells also resulted in increased bacterial localization in the cytosol, indicating that the role of TBK1 in maintaining vacuolar integrity is relevant in different cell types. Taken together, these data demonstrate a requirement for TBK1 in control of bacterial infection distinct from its established role in antiviral immunity.
Pediatric lymphomas in Brazil
Gualco, Gabriela;Klumb, Claudete E.;Barber, Glen N.;Weiss, Lawrence M.;Bacchi, Carlos E.;
Clinics , 2010, DOI: 10.1590/S1807-59322010001200008
Abstract: objective: this study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of brazil. methods: a retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. we believe that it represents the largest series of pediatric lymphomas presented from brazil. results: non-hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. mature cell lymphomas comprised 81% of the b-cell phenotype and 19% of the t-cell phenotype. hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. the geographic distribution showed 38.4% of the cases in the southeast region, 28.7% in the northeast, 16.1% in the south, 8.8% in the north, and 8% in the central-west region. the distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. among mature b-cell lymphomas, most of the cases were burkitt lymphomas (65%), followed by diffuse large b-cell lymphomas (24%). in the mature t-cell group, anaplastic large cell lymphoma, alk-positive was the most prevalent (57%), followed by peripheral t-cell lymphoma, then not otherwise specified (25%). in the group of classic hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). nodular lymphocyte predominance occurred more frequently than in other series. conclusion: some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the brazilian population in different regions.
Marshall Barberán,Pablo;
Estudios constitucionales , 2010, DOI: 10.4067/S0718-52002010000100003
Abstract: in this paper two objectives are sought. the first objective is disclosure statement and consists of two exercises. first, it outlines some of the key features of what comparative law has tended to call "horizontal effect of fundamental rights", attempting to clarify certain questions that can lead to misunderstandings. then it will outline the theories in comparative law, german and american, have realized that institution from an abstract point of view and will complement this vision with a corporate vision, explain or conform to what eventually will be a perspective of what that the horizontal effect of fundamental rights may or may not mean. the second objective is critical. it will be argued that any theory of horizontal effectiveness of fundamental rights is limited by the distribution of compentence between courts that apply the law and constitutional courts.
?Dilemas?: metodológicos y éticos en la investigación antropológica en Servicios de salud
Barber,Nélida Alicia;
Av?? , 2009,
Abstract: in this paper we examine some particularities of anthropological research in hospitality institutions, on the basis of fieldwork carries out in hospitals of the metropolitan and suburban areas of buenos aires. on one side, we focus on the institutional requirements for allowing access to the hospital and, on the other side, on the emotional and ethical commitments of researchers. in what concern to the former, we discuss the problematic arising from procuring authorization from the ethical research committee of the hospital to conduct a research in these premises. on the other hand, we discuss some ethic problems and dilemmas and we analyze the methodological and theoretical implications of such issues.
Marshall Barberán,Pablo;
Revista de derecho (Valdivia) , 2009, DOI: 10.4067/S0718-09502009000100004
Abstract: this article deals with the suffrage system reform being attemted at the present. in the first part the conceptual matter referring to the normative character that the act of voting possesses and must possess is revised, assuming the premise that it is a right and not an obligation. it is concluded that there is no conceptual contradiction in the figure of a right which exercise is mandatory. in the second part, the arguments used to justify the need to reform the suffrage regime are revised, concluding that the principle reasons that should be on the base of this kind of decision have not been explicit.
La soberanía popular como fundamento del orden estatal y como principio constitucional
Marshall Barberán,Pablo;
Revista de derecho (Valparaíso) , 2010, DOI: 10.4067/S0718-68512010000200008
Abstract: this work aims at presenting the origin and the basis of the principle of popular sovereignty, its role within the contemporaneous theory of the constitution and the meaning and extent that its constitutional enshrining has in chile. to do this, the role of popular sovereignty in each of the dimensions it is commonly used is analyzed: political theory, constitutional and dogmatic theory, as well as detecting the relationship among said dimensions.
El derecho a votar desde el extranjero
Marshall Barberán,Pablo;
Revista de derecho (Valdivia) , 2011, DOI: 10.4067/S0718-09502011000200006
Abstract: this paper presents certain elements, mainly taken from comparative law and political theory, which can make more intelligible the discussion on the vote from abroad in the chilean political system. the first part of this work shows the importance of discussing its foundation by clarifying some of its philosophical premises. the second part of this paper examines the constitutional reform bill that was rejected by congress, concluding that it was affected by significant theoretical problems. finally, the third part of the paper considers the particular elements that legislation on voting from abroad should consider.
Marshall Barberán,Pablo;
Revista de derecho (Valdivia) , 2008, DOI: 10.4067/S0718-09502008000100002
Abstract: this work elaborates on two relevant issues in constitutional law, by means of analysing a recent judicial decision. the first of those issues relates to the difficulty that arises when the application of a statute to a specific case results in an infringement of the constitution. the second topic refers to the constitutional principles that should guide and regulate the practice of electoral law, specially the manner in which broadcast time should be allocated between the various candidates. the main objective of this work is to set up a well defined conception of the principle of equal concern for political parties and independents.
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