bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rabies Virus Expressing Dendritic Cell-Activating Molecules Enhances the Innate and Adaptive Immune Response to Vaccination
Authors: Wen Yongjun , Wang Hualei , Wu Hua , Yang Fuhe , Tripp Ralph A. , Hogan Robert J. , Fu Zhen F. 
Published: November 2010

ABSTRACTOur previous studies indicated that recruitment and/or activation of dendritic cells (DCs) is important in enhancing the protective immune responses against rabies virus (RABV) (L. Zhao, H. Toriumi, H. Wang, Y. Kuang, X. Guo, K. Morimoto, and Z. F. Fu, J. Virol. 84:9642-9648). To address the importance of DC activation for RABV vaccine efficacy, the genes for several DC recruitment and/or activation molecules, e.g., granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-derived chemokine (MDC), and macrophage inflammatory protein 1α (MIP-1α), were individually cloned into RABV. The ability of these recombinant viruses to activate DCs was determinedin vitroandin vivo. Infection of mouse bone marrow-derived DCs with each of the recombinant viruses resulted in DC activation, as shown by increased surface expression of CD11c and CD86 as well as an increased level of alpha interferon (IFN-α) production compared to levels observed after infection with the parent virus. Intramuscular infection of mice with each of the viruses recruited and/or activated more DCs and B cells in the periphery than infection with the parent virus, leading to the production of higher levels of virus-neutralizing antibodies. Furthermore, a single immunization with recombinant RABV expressing GM-CSF or MDC protected significantly more mice against intracerebral challenge with virulent RABV than did immunization with the parental virus. Yet, these viruses did not show more virulence than the parent virus, since direct intracerebral inoculation with each virus at up to 1 × 107fluorescent focus units each did not induce any overt clinic symptom, such as abnormal behavior, or any neurological signs. Together, these data indicate that recombinant RABVs expressing these molecules activate/recruit DCs and enhance protective immune responses.
The Activator Protein 1 Binding Motifs within the Human Cytomegalovirus Major Immediate-Early Enhancer Are Functionally Redundant and Act in a Cooperative Manner with the NF-κB Sites during Acute Infection
Authors: Isern Elena , Gustems Montse , Messerle Martin , Borst Eva , Ghazal Peter , Angulo Ana 
Published: November 2010

ABSTRACT

Human cytomegalovirus (HCMV) infection causes a rapid induction of c-Fos and c-Jun, the major subunits of activator protein 1 (AP-1), which in turn have been postulated to activate the viral immediate-early (IE) genes. Accordingly, the major IE promoter (MIEP) enhancer, a critical control region for initiating lytic HCMV infection and reactivation from the latent state, contains one well-characterized AP-1 site and a second candidate interaction site. In this study we explored the role of these AP-1 elements in the context of the infection. We first show that the distal candidate AP-1 motif binds c-Fos/c-Jun heterodimers (AP-1 complex) and confers c-Fos/c-Jun-mediated activity to a core promoter. Site-directed mutagenesis studies indicate that both AP-1 response elements are critical for 12-
O
-tetradecanoylphorbol-13-acetate (TPA)-enhanced MIEP activity in transient-transfection assays. In marked contrast to the results obtained with the isolated promoter, disruption of the AP-1 recognition sites of the MIEP in the context of the infectious HCMV genome has no significant influence on the expression of the MIE protein IE1 or viral replication in different cell types. Moreover, a chimeric murine CMV driven by the HCMV MIEP (hMCMV-ES) with the two AP-1 binding sites mutated is not compromised in virulence, is able to grow and disseminate to different organs of the newborn mice as efficiently as the parental virus, and is competent in reactivation. We show, however, that combined inactivation of the enhancer AP-1 and NF-κB recognition sites leads to an attenuation of the hMCMV-ES in the neonatal murine infection model, not observed when each single element is abolished. Altogether, these results underline the functional redundancy of the MIEP elements, highlighting the plasticity of this region, which probably evolved to ensure maximal transcriptional performance across many diverse environments.
Coordinate Roles of Gag and RNA Helicase A in Promoting the Annealing of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRNA}_{3}^{\mathrm{Lys}}\) \end{document} to HIV-1 RNA
Authors: Xing Li , Liang Chen , Kleiman Lawrence 
Published: November 2010

ABSTRACT

RNA helicase A (RHA) has been shown to promote HIV-1 replication at both the translation and reverse transcription stages. A prerequisite step for reverse transcription involves the annealing of

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

, the primer for reverse transcription, to HIV-1 RNA.

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

annealing is a multistep process that is initially facilitated by Gag prior to viral protein processing. Herein, we report that RHA promotes this annealing through increasing both the quantity of

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

annealed by Gag and the ability of

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

to prime the initiation of reverse transcription. This improved annealing is the result of an altered viral RNA conformation produced by the coordinate action of Gag and RHA. Since RHA has been reported to promote the translation of unspliced viral RNA to Gag protein, our observations suggest that the conformational change in viral RNA induced by RHA and newly produced Gag may help facilitate the switch in viral RNA from a translational mode to one facilitating

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

annealing.
Factors predicting incorrect use of restraints by children travelling in cars: a cluster randomised observational study
Authors: Bilston Lynne E , Du Wei , Brown Julie 
Published: November 2010

BackgroundThe benefits of correctly using size-appropriate restraints for children travelling in cars are well established, and considerable research has focused on the determinants of appropriate restraint choice. There are few studies of the factors associated with incorrect use.ObjectiveTo determine predictors of incorrect restraint use by child occupants and how these differ from inappropriate use.MethodsA stratified multistage cluster sample of child occupants aged 0–10 years in New South Wales, Australia was used. Observation of restraint type and inspection of correctness of use was performed on arrival at schools, childcare centres, and child health clinics. An interview was conducted with the driver. Logistic regression was performed to estimate the effects of parental, family, and other characteristics on the likelihood of moderate or serious incorrect restraint use for restraint classes (rear/forward facing, booster, and seatbelt).ResultsSignificant factors varied depending on age and restraint class. Older child restraint users (OR per year of age 0.27, 95% CI 0.07 to 0.98) and seatbelt users (OR per year of age 0.54, 95% CI 0.45 to 0.64) were less likely to be incorrectly using their restraints than younger users. Child restraint and booster users from non-English speaking families were more likely to be incorrectly using their restraints. Having more children in the car appeared to reduce incorrect use for booster (OR 0.18, 95% CI 0.06 to 0.57) and seatbelt users (OR 0.39, 95% CI 0.16 to 0.93).ConclusionsThere is a need to reduce incorrect restraint use by both education and improved restraint design. Education aimed at reducing incorrect use may need to be targeted differently to appropriate use programmes, as the predictive factors differ.
Immunohistochemical assessment for Cdx2 expression in the Barrett metaplasia–dysplasia–adenocarcinoma sequence
Authors: Hayes Stephen , Ahmed Sajad , Clark Peter 
Published: November 2010

BackgroundBarrett oesophagus (BO) occurs as a consequence of prolonged gastro-oesophageal reflux and it may precede the development of oesophageal adenocarcinoma.AimsThe aim of this study was to accurately assess Cdx2 expression in the oesophageal metaplasia–dysplasia–adenocarcinoma sequence.MethodThe expression of the transcription factor Cdx2 in Barrett metaplasia, high-grade glandular dysplasia and adenocarcinoma was investigated using immunohistochemistry.ResultsThe results confirmed previous immunohistochemistry and PCR-based investigations, indicating that Cdx2 was expressed by intestinal metaplasia in the oesophagus. In addition, upregulation followed by linear downregulation of Cdx2 expression through the oesophageal metaplasia–dysplasia–adenocarcinoma sequence was demonstrated for the first time.ConclusionSuch downregulation of Cdx2 expression could be in keeping with a role as a tumour suppressor gene, but a simpler explanation would be downregulation of a differentiation marker.
Tamoxifen, Flaxseed, and the Lignan Enterolactone Increase Stroma- and Cancer Cell–Derived IL-1Ra and Decrease Tumor Angiogenesis in Estrogen-Dependent Breast Cancer
Authors: Lindahl Gabriel , Saarinen Niina , Abrahamsson Annelie , Dabrosin Charlotta 
Published: November 2010

Abstract
The proinflammatory cytokines IL-1α and IL-1β promote tumor angiogenesis that might be counteracted by the IL-1 receptor antagonist (IL-1Ra), anakinra, a clinically approved agent. A diet with high amounts of phytoestrogens, such as flaxseed (Flax), genistein (GEN), and the mammalian lignan enterolactone (ENL), may affect breast cancer progression in a similar fashion as the antiestrogen tamoxifen. Both cancer cells and tumor stroma may be targets for cancer therapy. By using microdialysis in a model of human breast cancers in nude mice, we could perform species-specific analyses of released proteins in the microenvironment. We show that tumors treated with tamoxifen and fed Flax or ENL exhibited decreased in vivo release of IL-1β derived from the murine stroma and decreased microvessel density whereas dietary GEN had no effects. Cancer cell–released IL-1Ra were approximately 5 times higher than stroma-derived IL-1Ra. Tamoxifen, Flax, and ENL increased IL-1Ra levels significantly whereas GEN did not. The tumor stroma contained macrophages, which expressed the estrogen receptor. In vitro, estradiol decreased IL-1Ra released from breast cancer cells and from cultured macrophages. IL-1Ra decreased endothelial cell proliferation significantly in vitro whereas breast cancer cell proliferation was unaffected in presence of estradiol. Finally, IL-1Ra therapy of tumor-bearing mice opposed estrogen-dependent breast cancer growth and decreased angiogenesis. We conclude that the release of IL-1s both by cancer cells and the stroma, where macrophages are a key component, may offer feasible targets for antiestrogen therapy and dietary interventions against breast cancer. Cancer Res; 71(1); 51–60. ©2011 AACR.
Impact ofABCB1Allelic Variants on QTc Interval Prolongation
Authors: Sissung Tristan M. , Gardner Erin R. , Piekarz Richard L. , Howden Reuben , Chen Xiaohong , Woo Sukyung , Franke Ryan , Clark James A. , Miller-DeGraff Laura , Steinberg Seth M. , Venzon David , Liewehr David , Kleeberger Steven R. , Bates Susan E. , Price Douglas K. , Rosing Douglas R. , Cabell Christopher , Sparreboom Alex , Figg William D. 
Published: November 2010

AbstractPurpose: Although the ABCB1 (P-glycoprotein) drug transporter is a constituent of several blood–tissue barriers (i.e., blood–brain and blood–nerve), its participation in a putative blood–heart barrier has been poorly explored. ABCB1 could decrease the intracardiac concentrations of drugs that cause QT prolongation and cardiotoxicity.Experimental Design: ABCB1-related romidepsin transport kinetics were explored in LLC-PK1 cells transfected with different ABCB1 genetic variants. ABCB1 plasma and intracardiac concentrations were determined in Abcb1a/1b (−/−) mice and wild-type FVB controls. These same mice were used to evaluate romidepsin-induced heart rate-corrected QT interval (QTc) prolongation over time. Finally, a cohort of 83 individuals with available QTcB and ABCB1 genotyping data were used to compare allelic variation in ABCB1 versus QTc-prolongation phenotype.Results: Here, we show that mice lacking the ABCB1-type P-glycoprotein have higher intracardiac concentrations of a model ABCB1 substrate, romidepsin, that correspond to changes in QT prolongation from baseline (ΔQTc) over time. Consistent with this observation, we also show that patients carrying genetic variants that could raise ABCB1 expression in the cardiac endothelium have lower ΔQTc following a single dose of romidepsin.Conclusions: To our knowledge, this is the first evidence that Abcb1-type P-glycoprotein can limit intracardiac exposure to a drug that mediates QT prolongation and suggests that certain commonly inherited polymorphisms in ABCB1 may serve as markers for QT prolongation following the administration of ABCB1-substrate drugs. Clin Cancer Res; 17(4); 937–46. ©2010 AACR.
Nitric Oxide–Donating Acetylsalicylic Acid Induces Apoptosis in Chronic Lymphocytic Leukemia Cells and Shows Strong Antitumor Efficacy In vivo
Authors: Razavi Regina , Gehrke Iris , Gandhirajan Rajesh Kumar , Poll-Wolbeck Simon Jonas , Hallek Michael , Kreuzer Karl-Anton 
Published: November 2010

Abstract
Purpose: Nitric oxide–donating acetylsalicylic acid (NO-ASA) has been shown to possess an antineoplastic effect in Wnt-/β-catenin–active cancers. As chronic lymphocytic leukemia (CLL) cells exhibit aberrantly active Wnt signaling, we investigated the effect of the para-isomer of NO-ASA on CLL cell survival in vitro and in a CLL-like xenograft mouse model.
Experimental Design: Apoptosis in primary CLL cells was determined by flow cytometric annexin V–FITC (fluorescein isothiocyanate)/PI (propidium iodide) staining and immunoblotting of caspases, poly(ADP-ribose) polymerase (PARP), and antiapoptotic proteins. Interference of NO-ASA with Wnt/β-catenin signaling was analyzed through immunoblots of different pathway members. Influence of caspase activation was investigated by pretreatment with a pan-caspase inhibitor. CLL-like JVM3 cells were subcutaneously inoculated into irradiated nude mice that were treated with 100 mg of para-NO-ASA/kg of body weight p.o. (by mouth) for 21 days.
Results: para-NO-ASA induced apoptosis in CLL cells with an LC50 (lethal concentration) of 8.72 + 0.04 μmol/L, whereas healthy blood cells were not affected. Furthermore, the compound induced caspase 9, caspase 3, and PARP cleavage. In addition, cleavage of β-catenin and downregulation of β-catenin/lymphoid enhancer factor (Lef)–1 targets was observed. para-NO-ASA demonstrated strong antitumor efficacy in the xenograft mouse model with a tumor inhibtion rate of 83.4%. During therapy, no gross toxicity could be observed.
Conclusions: para-NO-ASA selectively induces apoptosis in primary CLL cells and efficiently reduces tumor growth in a CLL-like xenograft model. As NO-ASA is orally available and is generally well tolerated, para-NO-ASA might be a promising new compound for CLL therapy. Clin Cancer Res; 17(2); 286–93. ©2010 AACR.
Outcome by Stroke Etiology in Patients Receiving Thrombolytic Treatment
Authors: Mustanoja Satu , Meretoja Atte , Putaala Jukka , Viitanen Varpu , Curtze Sami , Atula Sari , Artto Ville , Häppölä Olli , Kaste Markku ,   for the Helsinki Stroke Thrombolysis Registry Group
Published: November 2010

Background and Purpose—
Treating ischemic stroke with thrombolytic therapy is effective and safe, but limited data exist on its efficacy and safety in different etiologic subtypes.

Methods—
Patients with acute ischemic stroke treated with intravenous thrombolysis between 1995 and 2008 at our hospital were classified according to the Trial of ORG 10172 in Acute Stroke Treatment criteria based on diagnostic evaluation. Clinical outcome of the stroke subtypes by 3-month modified Rankin Scale was compared by multivariate logistic regression. A good outcome was defined as modified Rankin Scale ≤2. Symptomatic intracranial hemorrhage was defined according to both National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study criteria.

Results—
Of the 957 eligible patients, 41% (389) had cardioembolisms, 23% (217) large-artery atherosclerosis, and 11% (101) small-vessel disease (SVD). A good outcome was more common in SVD than in the other subtypes. Patients with SVD were more often male (64% versus 54%), had a lower baseline National Institutes of Health Stroke Scale score, lower mortality rate, and experienced no symptomatic intracranial hemorrhage. Patients with SVD had a prior stroke more often (20% versus 11%), whereas hypertension, diabetes, hypercholesterolemia, and transient ischemic attacks were equally distributed in all subtypes. Patients with SVD had a better outcome even after adjusting for baseline National Institutes of Health Stroke Scale and glucose level, age, and hyperdense artery sign (OR, 1.81; 1.01 to 3.23). In the adjusted multivariate model, other etiologic groups showed no significant correlation to good outcome.

Conclusions—
Patients with SVD were spared from bleeding complications and had the best outcome even after adjustment for confounding factors.
A Mouse Model of Hemorrhagic Transformation by Delayed Tissue Plasminogen Activator Administration After In Situ Thromboembolic Stroke
Authors: García-Yébenes Isaac , Sobrado Mónica , Zarruk Juan G. , Castellanos Mar , Pérez de la Ossa Natalia , Dávalos Antoni , Serena Joaquín , Lizasoain Ignacio , Moro María A. 
Published: November 2010

Background and Purpose—
Thrombolytic treatment with tissue plasminogen activator (tPA) improves outcome of patients with stroke who can be treated within 3 hours of symptom onset. However, delayed treatment with tPA leads to increased risk of hemorrhagic transformation and can result in enhanced brain injury. The purpose of this study is to validate a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA.

Methods—
Mice were anesthetized and thrombin was injected into the middle cerebral artery to induce the formation of a clot as described by Orset et al. To induce reperfusion, tPA (10 mg/kg) was intravenously administered 20 minutes or 3 hours after thrombin injection.

Results—
Thrombin produced a clot in 83.1% of the animals, which caused focal ischemia determined 24 hours after the injection. Different degrees of bleeding were found in the middle cerebral artery occlusion group, including hemorrhagic infarction type 1 (HI-1) in 46.2%, hemorrhagic infarction type 2 (HI-2) in 30.8% and parenchymal hemorrhage type 1 in 23.0%. Administration of tPA 20 minutes after the occlusion produced an effective reperfusion in 62.5% of the animals and reduced both infarct volume and appearance of severe hemorrhage (10% nonhemorrhage, 80% HI-1 and 10% HI-2). However, administration of tPA 3 hours after the occlusion led to effective reperfusion in 47.1% of the animals, did not reduce infarct volume, caused hemorrhagic transformation (25% HI-1, 37.5% HI-2, and 37.5% parenchymal hemorrhage type 1), and increased hemorrhage and brain swelling.

Conclusions—
We have set up a reproducible mouse model of hemorrhagic transformation associated with delayed administration of tPA similar to that observed in humans.
Navigating “Deuteronomistic History” as Cultural Memory
Authors: Forget Gaétane-Diane 
Published: November 2010

AbstractScribal tradents have been the custodians of identity. Through memory and meaning an identity was born and within their work the reader finds the pillars of mnemonic socialization. The so-called Deuteronomistic History, as a cultural memory, is a form of crafting and protecting an identity.
Involuntary admission in Greece: A prospective national study of police involvement and client characteristics affecting emergency assessment
Authors: Douzenis Athanassios , Michopoulos Ioannis , Economou Marina , Rizos Emmanouil , Christodoulou Christos , Lykouras Lefteris 
Published: November 2010

Background and aim: Mental health legislation varies considerably from one country to the other. This study aims to describe the characteristics of the individuals who are brought in by the police for psychiatric assessment and the police involvement in this procedure in Greece. Method: Prospective study of the incident books of the police departments throughout Greece concerning involuntary psychiatric admissions. These books were completed by the police officers who brought the individuals for involuntary psychiatric examination. Results: In total, 2,038 involuntary assessments were evaluated and examined in relationship to the demographic characteristics of the examined individuals. The main findings are as follows. Males were more often assessed (69%) at a younger age than females ( p < 0.001). The majority of the assessments led to involuntary admission (87.5%). Immigrant status did not lead to increased involuntary commitment. The chance for involuntary admission was greater for younger Greek nationals offering resistance. An unexpected finding is that police officers were unnecessarily present in almost half of the mental health assessments (49.4%). Conclusion: The psychiatrists in Greece who perform mental health assessments under the Greek Mental Health Law admit the majority of individuals. They also accept the presence of a police officer during the assessment more often than expected. This issue needs immediate addressing by means of better training and support of psychiatrists.