bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEAD‐box proteins, like Leishmania eIF4A, modulate interleukin (IL)‐12, IL‐10 and tumour necrosis factor‐alpha production by human monocytes
Authors: Barhoumi M. , Meddeb‐Garnaoui A. , Tanner N. K. , Banroques J. , Kaabi B. , Guizani I. 
Published: January 2013

SummaryPreviously we showed that His‐tagged, recombinant, Leishmania infantum eukaryotic initiation factor (LeIF) was both an RNA‐dependent ATPase and an ATP‐dependent RNA helicase in vitro, as described for other members of the DEAD‐box helicase family. In addition, we showed that LeIF induces the production of IL‐12, IL‐10, and TNF‐α by human monocytes. This study aims to characterize the cytokine‐inducing activity in human monocytes of several proteins belonging to the DEAD‐box family from mammals and yeast. All tested proteins contained the 11 conserved motifs (Q, I, Ia, GG Ib, II, III, IV, QxxR, V and VI) characteristic of DEAD‐box proteins, but they have different biological functions and different percentages of identities with LeIF. We show that these mammalian or yeast recombinant proteins also are able to induce IL‐12, IL‐10 and TNF‐α secretion by monocytes of healthy human subjects. This cytokine‐inducing activity is proteinase K sensitive and polymyxin B resistant. Our results show that the induction of cytokines in human monocytes is not unique to the protein LeIF of Leishmania, and it suggests that the activity of certain DEAD‐box proteins can be exploited as adjuvant and/or to direct immune responses towards a Th1 profile in vaccination or immunotherapy protocols.
The Expression of Aryl Hydrocarbon Receptor in Porcine Ovarian Cells
Authors: Jablonska O , Ciereszko RE 
Published: January 2013

ContentsThe aryl hydrocarbon receptor (AHR) is an intracellular transcription factor best known for mediating the toxicity of dioxins. The AHR is phylogenetically highly conserved among invertebrates and vertebrates and may play a significant role in the regulation of physiological processes including female reproduction. This study was performed to determine the partial nucleotide sequence of porcine AHR and to evaluate the AHR mRNA (real‐time PCR) and AHR protein (Western blot) expression in granulosa and theca interna cells harvested from medium (3–6 mm) and pre‐ovulatory (≥8 mm) follicles as well as in luteal cells obtained from corpora lutea collected during the mid‐luteal phase (days: 8–10) of the porcine oestrous cycle. In the study, the partial nucleotide sequence of porcine AHR containing 1021 bp (GenBank accession no: HM488957.1) was determined. The AHR transcript and protein were found in all ovarian cells obtained during both phases of the porcine oestrous cycle. The highest AHR transcript level was detected in theca interna cells isolated from pre‐ovulatory follicles as well as in luteal cells. Higher AHR protein expression was found in granulosa cells isolated from pre‐ovulatory follicles in comparison with all remaining cell types. The presence of AHR in the examined ovarian cells may account for their sensitivity to some environmental pollutants. Moreover, the differences found in AHR mRNA expression between granulosa and theca cells as well as between cells originating from follicles of different size suggest the involvement of AHR in the modulation of reproductive processes in the porcine ovary.
Listeria monocytogenes in donated platelets: a potential transfusion‐transmitted pathogen intercepted through screening
Authors: Menon Manoj , Graves Lewis , McCombs Katherine , Hise Kelly , Silk Benjamin , Kuehnert Matthew , Lynch Michael 
Published: January 2013

BackgroundBacterial contamination of blood components is a potentially life‐threatening complication of transfusions. In October 2005, the Centers for Disease Control and Prevention (CDC) noted four Listeria monocytogenes (Lm) isolates cultured from four different units of donated apheresis platelets (PLTs) among Lm isolates sent to the CDC National Listeria Reference Laboratory for subtyping as part of routine surveillance activities.Study Design and MethodsWe describe an investigation to determine possible common sources of infection among donors or factors associated with PLT collection or storage and to determine whether human transfusion‐associated listeriosis cases had been reported. We also reviewed all isolates with PLTs as a source sent to the CDC National Listeria Reference Laboratory between November 1, 2005, and December 31, 2011.ResultsEach PLT donor–associated isolate had a distinct pulsed‐field gel electrophoresis pattern combination. Other than these four cases, no other cases of Lm‐contaminated PLTs were identified by the American Red Cross or by CDC during 2005. However, two additional cases of Lm isolated from donated PLTs were detected, one in 2008 and one in 2011.ConclusionAlthough the source of contamination for these PLT units is unclear, and a source common to all units was not identified, this investigation underscores the value of screening for bacterial contaminants of PLTs.
Transfusion‐transmitted human T‐lymphotropic virus Type I infection in a United States military emergency whole blood transfusion recipient in Afghanistan, 2010
Authors: Hakre Shilpa , Manak Mark M. , Murray Clinton K. , Davis Kenneth W. , Bose Meera , Harding Aaron J. , Maas Peter R. , Jagodzinski Linda L. , Kim Jerome H. , Michael Nelson L. , Rentas Francisco J. , Peel Sheila A. , Scott Paul T. , Tovanabutra Sodsai 
Published: January 2013

BackgroundThe United States introduced human T‐lymphotropic virus Type I (HTLV‐I) screening of blood donors in 1988. The US military uses freshly collected blood products for life‐threatening injuries when available stored blood components in theater have been exhausted or when these components are unsuccessful for resuscitation. These donors are screened after donation by the Department of Defense (DoD) retrospective testing program. All recipients of blood collected in combat are tested according to policy soon after and at 3, 6, and 12 months after transfusion.Case ReportA 31‐year‐old US Army soldier tested positive for HTLV‐I 44 days after receipt of emergency blood transfusions for severe improvised explosive device blast injuries. One donor's unit tested HTLV‐I positive on the DoD‐mandated retrospective testing. Both the donor and the recipient tested reactive with enzyme immunoassay and supplemental confirmation by HTLV‐I Western blot. The donor and recipient reported no major risk factors for HTLV‐I. Phylogenetic analysis of HTLV‐I sequences indicated Cosmopolitan subtype, Subgroup B infections. Comparison of long terminal repeat and env sequences revealed molecular genetic linkage of the viruses from the donor and recipient.ConclusionThis case is the first report of transfusion transmission of HTLV‐I in the US military during combat operations. The emergency fresh whole blood policy enabled both the donor and the recipient to be notified of their HTLV‐I infection. While difficult in combat, predonation screening of potential emergency blood donors with Food and Drug Administration–mandated infectious disease testing as stated by the DoD Health Affairs policy should be the goal of every facility engaged with emergency blood collection in theater.
Sequencing-Based Genotyping of Mixed Human Papillomavirus Infections by Use of RipSeq Software
Authors: Tardif Keith D. , Simmon Keith E. , Kommedal Øyvind , Pyne Michael T. , Schlaberg Robert 
Published: January 2013

ABSTRACT
Sequencing-based pathogen identification directly from clinical specimens requires time-consuming interpretation, especially with mixed chromatograms when multiple microorganisms are detected. We assessed RipSeq Mixed software for human papillomavirus (HPV) genotyping by comparison to the linear array HPV genotyping assay. RipSeq Mixed provided rapid, sequencing-based HPV typing for single-type infections and coinfections with 2 types.
Targeting IκB Proteins for HIV Latency Activation: the Role of Individual IκB and NF-κB Proteins
Authors: Fernandez Guerau , Zaikos Thomas D. , Khan Sohrab Z. , Jacobi Ashley M. , Behlke Mark A. , Zeichner Steven L. 
Published: January 2013

ABSTRACTLatently infected cell reservoirs represent the main barrier to HIV eradication. Combination antiretroviral therapy (cART) effectively blocks viral replication but cannot purge latent provirus. One approach to HIV eradication could include cART to block new infections plus an agent to activate latent provirus. NF-κB activation induces HIV expression, ending latency. Before activation, IκB proteins sequester NF-κB dimers in the cytoplasm. Three canonical IκBs, IκBα, IκBβ, and IκBε, exist, but the IκB proteins' role in HIV activation regulation is not fully understood. We studied the effects on HIV activation of targeting IκBs by single and pairwise small interfering RNA (siRNA) knockdown. After determining the relative abundance of the IκBs, the relative abundance of NF-κB subunits held by the IκBs, and the kinetics of IκB degradation and resynthesis following knockdown, we studied HIV activation by IκB knockdown, in comparison with those of known HIV activators, tumor necrosis factor alpha (TNF-α), tetradecanoyl phorbol acetate (TPA), and trichostatin A (TSA), in U1 monocytic and J-Lat 10.6 lymphocytic latently infected cells. We found that IκBα knockdown activated HIV in both U1 and J-Lat 10.6 cells, IκBβ knockdown did not activate HIV, and, surprisingly, IκBε knockdown produced the most HIV activation, comparable to TSA activation. Our data show that HIV reactivation can be triggered by targeting two different IκB proteins and that IκBε may be an effective target for HIV latency reactivation in T-cell and macrophage lineages. IκBε knockdown may offer attractive therapeutic advantages for HIV activation because it is not essential for mammalian growth and development and because new siRNA delivery strategies may target siRNAs to HIV latently infected cells.
Modeling the Acute and Chronic Phases of Theiler Murine Encephalomyelitis Virus Infection
Authors: Zhang Jingshan , Lipton Howard L. , Perelson Alan S. , Dahari Harel 
Published: January 2013

ABSTRACTTheiler murine encephalomyelitis virus (TMEV) infection of a mouse's central nervous system is biphasic: first the virus infects motor neurons (acute phase), and this is followed by a chronic phase in which the virus infects glial cells (primarily microglia and macrophages [Mϕ]) of the spinal cord white matter, leading to inflammation and demyelination. As such, TMEV-induced demyelinating disease in mice provides a highly relevant experimental animal model for multiple sclerosis. Mathematical models have proven valuable in understanding thein vivodynamics of persistent virus infections, such as HIV-1, hepatitis B virus, and hepatitis C virus infections. However, viral dynamic modeling has not been used for understanding TMEV infection. We constructed the first mathematical model of TMEV-host kinetics during acute and early chronic infections in mice and fit measured viral kinetic data with the model. The data fitting allowed us to estimate several unknown parameters, including the following: the rate of infection of neurons, 0.5 × 10−8to 5.6 × 10−8day−1; the percent reduction of the infection rate due to the presence of virus-specific antibodies, which reaches 98.5 to 99.9% after day 15 postinfection (p.i.); the half-life of infected neurons, 0.1 to 1.2 days; and a cytokine-enhanced macrophage source rate of 25 to 350 Mϕ/day into the spinal cord starting at 10.9 to 12.9 days p.i. The model presented here is a first step toward building a comprehensive model for TMEV-induced demyelinating disease. Moreover, the model can serve as an important tool in understanding TMEV infectious mechanisms and may prove useful in evaluating antivirals and/or therapeutic modalities to prevent or inhibit demyelination.
SMC1-Mediated Intra-S-Phase Arrest Facilitates Bocavirus DNA Replication
Authors: Luo Yong , Deng Xuefeng , Cheng Fang , Li Yi , Qiu Jianming 
Published: January 2013

ABSTRACT

Activation of a host DNA damage response (DDR) is essential for DNA replication of minute virus of canines (MVC), a member of the genus
Bocavirus
of the
Parvoviridae
family; however, the mechanism by which DDR contributes to viral DNA replication is unknown. In the current study, we demonstrate that MVC infection triggers the intra-S-phase arrest to slow down host cellular DNA replication and to recruit cellular DNA replication factors for viral DNA replication. The intra-S-phase arrest is regulated by ATM (ataxia telangiectasia-mutated kinase) signaling in a p53-independent manner. Moreover, we demonstrate that SMC1 (structural maintenance of chromosomes 1) is the key regulator of the intra-S-phase arrest induced during infection. Either knockdown of SMC1 or complementation with a dominant negative SMC1 mutant blocks both the intra-S-phase arrest and viral DNA replication. Finally, we show that the intra-S-phase arrest induced during MVC infection was caused neither by damaged host cellular DNA nor by viral proteins but by replicating viral genomes physically associated with the DNA damage sensor, the Mre11-Rad50-Nbs1 (MRN) complex. In conclusion, the feedback loop between MVC DNA replication and the intra-S-phase arrest is mediated by ATM-SMC1 signaling and plays a critical role in MVC DNA replication. Thus, our findings unravel the mechanism underlying DDR signaling-facilitated MVC DNA replication and demonstrate a novel strategy of DNA virus-host interaction.
Interactions of the Kaposi's Sarcoma-Associated Herpesvirus Nuclear Egress Complex: ORF69 Is a Potent Factor for Remodeling Cellular Membranes
Authors: Luitweiler Eric M. , Henson Brandon W. , Pryce Erin N. , Patel Varun , Coombs Gavin , McCaffery J. Michael , Desai Prashant J. 
Published: January 2013

ABSTRACT
All herpesviruses encode a complex of two proteins, referred to as the nuclear egress complex (NEC), which together facilitate the exit of assembled capsids from the nucleus. Previously, we showed that the Kaposi's sarcoma-associated herpesvirus (KSHV) NEC specified by the ORF67 and ORF69 genes when expressed in insect cells using baculoviruses for protein expression forms a complex at the nuclear membrane and remodels these membranes to generate nuclear membrane-derived vesicles. In this study, we have analyzed the functional domains of the KSHV NEC proteins and their interactions. Site-directed mutagenesis of gammaherpesvirus conserved residues revealed functional domains of these two proteins, which in many cases abolish the formation of the NEC and remodeling of nuclear membranes. Small in-frame deletions within ORF67 in all cases result in loss of the ability of the mutant protein to induce cellular membrane proliferation as well as to interact with ORF69. Truncation of the C terminus of ORF67 that resides in the perinuclear space does not impair the functions of ORF67; however, deletion of the transmembrane domain of ORF67 produces a protein that cannot induce membrane proliferation but can still interact with ORF69 in the nucleus and can be tethered to the nuclear membrane by virtue of its interaction with the wild-type-membrane-anchored ORF67. In-frame deletions in ORF69 have varied effects on NEC formation, but all abolish remodeling of nuclear membranes into circular structures. One mutant interacts with ORF67 as well as the wild-type protein but cannot function in membrane curvature and fission events that generate circular vesicles. These studies genetically confirm that ORF67 is required for cellular membrane proliferation and that ORF69 is the factor required to remodel these duplicated membranes into circular-virion-size vesicles. Furthermore, we also investigated the NEC encoded by Epstein-Barr virus (EBV). The EBV complex comprised of BFRF1 and BFLF2 was visualized at the nuclear membrane using autofluorescent protein fusions. BFRF1 is a potent inducer of membrane proliferation; however, BFLF2 cannot remodel these membranes into circular structures. What was evident is the superior remodeling activity of ORF69, which could convert the host membrane proliferations induced by BFRF1 into circular structures.
Human Papillomavirus Episome Stability Is Reduced by Aphidicolin and Controlled by DNA Damage Response Pathways
Authors: Edwards Terri G. , Helmus Michael J. , Koeller Kevin , Bashkin James K. , Fisher Chris 
Published: January 2013

ABSTRACT
A highly reproducible quantitative PCR (Q-PCR) assay was used to study the stability of human papillomavirus (HPV) in undifferentiated keratinocytes that maintain viral episomes. The term “stability” refers to the ability of episomes to persist with little copy number variation in cells. In investigating the mechanism of action of PA25, a previously published compound that destabilizes HPV episomes, aphidicolin was also found to markedly decrease episome levels, but via a different pathway from that of PA25. Since aphidicolin is known to activate DNA damage response (DDR) pathways, effects of inhibitors and small interfering RNAs (siRNAs) acting within DDR pathways were investigated. Inhibitors of Chk1 and siRNA directed against ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia Rad3-related (ATR) pathways significantly reduced viral episomes, suggesting that these pathways play a role in maintaining HPV episome stability. Inhibitors of Chk2 and DNA-PK had no effect on episome levels. Pharmacological inhibition of ATM proteins had no effect on episome levels, but ATM knockdown by siRNA significantly reduced episome levels, suggesting that ATM proteins are playing an important role in HPV episome stability that does not require kinase activity. These results outline two pathways that trigger episome loss from cells and suggest the existence of a little-understood mechanism that mediates viral DNA elimination. Together, our results also indicate that HPV episomes have a stability profile that is remarkably similar to that of fragile sites; these similarities are outlined and discussed. This close correspondence may influence the preference of HPV for integration into fragile sites.
Methodology of a large prospective, randomised, open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the standard care versus celecoxib outcome trial (SCOT)
Authors: MacDonald Thomas M , Mackenzie Isla S , Wei Li , Hawkey Christopher J , Ford Ian 
Published: January 2013

IntroductionCyclooxygenase 2 (COX-2) inhibitors have less upper gastrointestinal toxicity than traditional non-steroidal anti-inflammatory drugs (NSAIDs). However, both COX-2 inhibitors and traditional NSAIDs may be associated with adverse cardiovascular side effects. Data from randomised and observational studies suggest that celecoxib has similar cardiovascular toxicity to traditional NSAIDs. The overall safety balance of a strategy of celecoxib therapy versus traditional NSAID therapy is unknown. The European Medicines Agency requested studies of the cardiovascular safety of celecoxib within Europe. The Standard care versus Celecoxib Outcome Trial (SCOT) compares the cardiovascular safety of celecoxib with traditional NSAID therapy in the setting of the European Union healthcare system.Methods and analysisSCOT is a large streamlined safety study conducted in Scotland, England, Denmark and the Netherlands using the Prospective Randomised Open Blinded Endpoint design. Patients aged over 60 years with osteoarthritis or rheumatoid arthritis, free from established cardiovascular disease and requiring chronic NSAID therapy, are randomised to celecoxib or their previous traditional NSAID. They are then followed up for events by record-linkage within their normal healthcare setting. The hypothesis is non-inferiority with a confidence limit of 1.4. The primary endpoint is the first occurrence of hospitalisation or death for the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are (1) first hospitalisation or death for upper gastrointestinal ulcer complications (bleeding, perforation or obstruction); (2) first occurrence of hospitalised upper gastrointestinal ulcer complications or APTC endpoint; (3) first hospitalisation for heart failure; (4) first hospitalisation for APTC endpoint plus heart failure; (5) all-cause mortality and (6) first hospitalisation for new or worsening renal failure.Ethics and disseminationSCOT has been approved by the relevant ethics committees. The trial results will be published in a peer-reviewed scientific journal.Clinical trials registration numberClinicaltrials.gov (NCT00447759).
Management of vasospasm in ruptured unsecured intracranial vascular lesions: review of 10 cases
Authors: Serrone Joseph , Jimenez Lincoln , Andaluz Norberto , Abruzzo Todd A , Zuccarello Mario , Ringer Andrew J 
Published: January 2013

IntroductionRisks associated with endovascular management remain unaddressed for post-hemorrhagic cerebral vasospasm (PHCV) caused by pathologies that cannot be secured or identified before vasospasm treatment. This retrospective study reviews our 10 year experience in the difficult scenario of subarachnoid hemorrhage (SAH) with vasospasm, including intra-arterial vasodilators or percutaneous transluminal angioplasty (PTA) to vessels feeding a ruptured unsecured lesion.Methods10 SAH patients with ruptured unsecured vascular lesions underwent 44 endovascular treatments for PHCV (2002–2011). We defined unsecured as an untreated aneurysm/dissection, incompletely coiled aneurysm, dissection covered with self-expanding nitinol stents, or angiographically negative SAH. Treatments were categorized by location of the ruptured unsecured (partial or complete) lesion relative to the vessel treated for vasospasm.ResultsOur 10 patients with four aneurysms, four dissections, and two angiographically negative SAH accounted for 10.3% of SAH patients who underwent angiography for vasospasm. No procedure related complications occurred when treating vessels not supplying the index lesion or with angiographically negative SAH. Of the endovascular treated vessels supplying partially secured lesions, one (6.3%) fatal complication occurred; none of these patients receiving only vasodilators had complications. With endovascular treatment of PHCV with completely unsecured lesions, one (33%) complication was fatal.ConclusionsEndovascular treatment appeared safe for PHCV for vessels not supplying the index arterial lesion and for angiographically negative SAH. Vasodilators were safe for vessels harboring partially secured, ruptured lesions (eg, incompletely coiled aneurysms, stented dissections). Following two major complications, the safety of administering vasodilators or performing PTA to vessels supplying completely unsecured vascular lesions remains inconclusive and should be used cautiously.