bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Cooperation between Human Adenovirus Type 5 Early Region 4, Open Reading Frame 6 Protein, and Cellular Homeobox Protein HoxB7
Authors: Müller Daniela , Schreiner Sabrina , Schmid Melanie , Groitl Peter , Winkler Michael , Dobner Thomas 
Published: May 2012

ABSTRACT
Human adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional early viral protein promoting efficient replication and progeny production. E4orf6 complexes with E1B-55K to assemble cellular proteins into a functional E3 ubiquitin ligase complex that not only mediates proteasomal degradation of host cell substrates but also facilitates export of viral late mRNA to promote efficient viral protein expression and host cell shutoff. Recent findings defined the role of E4orf6 in RNA splicing independent of E1B-55K binding. To reveal further functions of the early viral protein in infected cells, we used a yeast two-hybrid system and identified the homeobox transcription factor HoxB7 as a novel E4orf6-associated protein. Using a HoxB7 knockdown cell line, we observed a positive role of HoxB7 in adenoviral replication. Our experiments demonstrate that the absence of HoxB7 leads to inefficient viral progeny production, as HAdV5 gene expression is highly regulated by HoxB7-mediated activation of various adenoviral promoters. We have thus identified a novel role of E4orf6 in HAdV5 gene transcription via regulation of homeobox protein-dependent modulation of viral promoter activity.
A Human Coronavirus Responsible for the Common Cold Massively Kills Dendritic Cells but Not Monocytes
Authors: Mesel-Lemoine Mariana , Millet Jean , Vidalain Pierre-Olivier , Law Helen , Vabret Astrid , Lorin Valérie , Escriou Nicolas , Albert Matthew L. , Nal Béatrice , Tangy Frédéric 
Published: May 2012

ABSTRACTHuman coronaviruses are associated with upper respiratory tract infections that occasionally spread to the lungs and other organs. Although airway epithelial cells represent an important target for infection, the respiratory epithelium is also composed of an elaborate network of dendritic cells (DCs) that are essential sentinels of the immune system, sensing pathogens and presenting foreign antigens to T lymphocytes. In this report, we show thatin vitroinfection by human coronavirus 229E (HCoV-229E) induces massive cytopathic effects in DCs, including the formation of large syncytia and cell death within only few hours. In contrast, monocytes are much more resistant to infection and cytopathic effects despite similar expression levels of CD13, the membrane receptor for HCoV-229E. While the differentiation of monocytes into DCs in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 requires 5 days, only 24 h are sufficient for these cytokines to sensitize monocytes to cell death and cytopathic effects when infected by HCoV-229E. Cell death induced by HCoV-229E is independent of TRAIL, FasL, tumor necrosis factor alpha, and caspase activity, indicating that viral replication is directly responsible for the observed cytopathic effects. The consequence of DC death at the early stage of HCoV-229E infection may have an impact on the early control of viral dissemination and on the establishment of long-lasting immune memory, since people can be reinfected multiple times by HCoV-229E.
HIV-1 gp120 Vaccine Induces Affinity Maturation in both New and Persistent Antibody Clonal Lineages
Authors: Moody M. Anthony , Yates Nicole L. , Amos Joshua D. , Drinker Mark S. , Eudailey Joshua A. , Gurley Thaddeus C. , Marshall Dawn J. , Whitesides John F. , Chen Xi , Foulger Andrew , Yu Jae-Sung , Zhang Ruijun , Meyerhoff R. Ryan , Parks Robert , Scull Julia Cavanaugh , Wang Lu , Vandergrift Nathan A. , Pickeral Joy , Pollara Justin , Kelsoe Garnett , Alam S. Munir , Ferrari Guido , Montefiori David C. , Voss Gerald , Liao Hua-Xin , Tomaras Georgia D. , Haynes Barton F. 
Published: May 2012

ABSTRACT

Most antibodies that broadly neutralize HIV-1 are highly somatically mutated in antibody clonal lineages that persist over time. Here, we describe the analysis of human antibodies induced during an HIV-1 vaccine trial (GSK PRO HIV-002) that used the clade B envelope (Env) gp120 of clone W6.1D (gp120
W6.1D
). Using dual-color antigen-specific sorting, we isolated Env-specific human monoclonal antibodies (MAbs) and studied the clonal persistence of antibodies in the setting of HIV-1 Env vaccination. We found evidence of V
H
somatic mutation induced by the vaccine but only to a modest level (3.8% ± 0.5%; range 0 to 8.2%). Analysis of 34 HIV-1-reactive MAbs recovered over four immunizations revealed evidence of both sequential recruitment of naïve B cells and restimulation of previously recruited memory B cells. These recombinant antibodies recapitulated the anti-HIV-1 activity of participant serum including pseudovirus neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC). One antibody (3491) demonstrated a change in specificity following somatic mutation with binding of the inferred unmutated ancestor to a linear C2 peptide while the mutated antibody reacted only with a conformational epitope in gp120 Env. Thus, gp120
W6.1D
was strongly immunogenic but over four immunizations induced levels of affinity maturation below that of broadly neutralizing MAbs. Improved vaccination strategies will be needed to drive persistent stimulation of antibody clonal lineages to induce affinity maturation that results in highly mutated HIV-1 Env-reactive antibodies.
Activation of Cap-Dependent Translation by Mucosal Human Papillomavirus E6 Proteins Is Dependent on the Integrity of the LXXLL Binding Motif
Authors: Spangle Jennifer M. , Ghosh-Choudhury Nayana , Munger Karl 
Published: May 2012

ABSTRACT
The human papillomavirus (HPV) type 16 (HPV16) E6 protein can stimulate mechanistic target of rapamycin complex 1 (mTORC1) signaling and cap-dependent translation through activation of the PDK1 and mTORC2 kinases. Here we report that HPV18 E6 also enhances cap-dependent translation. The integrity of LXXLL and PDZ protein binding domains is important for activation of cap-dependent translation by high-risk mucosal HPV E6 proteins. Consistent with this model, low-risk mucosal HPV6b and HPV11 E6 proteins, which do not contain a PDZ protein binding motif, also activate cap-dependent translation and mTORC1, albeit at a lower efficiency than high-risk HPV E6 proteins. In contrast, cutaneous HPV5 and HPV8 E6 proteins, which lack LXXLL and PDZ motif protein binding, do not enhance cap-dependent translation. Mutagenic analyses of low-risk HPV E6 proteins revealed that association with the LXXLL motif containing ubiquitin ligase E6AP (UBE3A) correlates with activation of cap-dependent translation. Hence, activation of mTORC1 and cap-dependent translation may be important for the viral life cycle in specific epithelial tissue types and contribute to cellular transformation in cooperation with other biological activities of high-risk HPV E6-containing proteins.
The Human T-Lymphotropic Virus Type 1 Tax Protein Inhibits Nonsense-Mediated mRNA Decay by Interacting with INT6/EIF3E and UPF1
Authors: Mocquet Vincent , Neusiedler Julia , Rende Francesca , Cluet David , Robin Jean-Philippe , Terme Jean-Michel , Duc Dodon Madeleine , Wittmann Jürgen , Morris Christelle , Le Hir Hervé , Ciminale Vincenzo , Jalinot Pierre 
Published: May 2012

ABSTRACT
In this report, we analyzed whether the degradation of mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was affected in human T-lymphotropic virus type 1 (HTLV-1)-infected cells. This pathway was indeed strongly inhibited in C91PL, HUT102, and MT2 cells, and such an effect was also observed by the sole expression of the Tax protein in Jurkat and HeLa cells. In line with this activity, Tax binds INT6/EIF3E (here called INT6), which is a subunit of the translation initiation factor eukaryotic initiation factor 3 (eIF3) required for efficient NMD, as well as the NMD core factor upstream frameshift protein 1 (UPF1). It was also observed that Tax expression alters the morphology of processing bodies (P-bodies), the cytoplasmic structures which concentrate RNA degradation factors. The presence of UPF1 in these subcellular compartments was increased by Tax, whereas that of INT6 was decreased. In line with these effects, the level of the phosphorylated form of UPF1 was increased in the presence of Tax. Analysis of several mutants of the viral protein showed that the interaction with INT6 is necessary for NMD inhibition. The alteration of mRNA stability was observed to affect viral transcripts, such as that coding for the HTLV-1 basic leucine zipper factor (HBZ), and also several cellular mRNAs sensitive to the NMD pathway. Our data indicate that the effect of Tax on viral and cellular gene expression is not restricted to transcriptional control but can also involve posttranscriptional regulation.
A dedicated inflammatory bowel disease service quantitatively and qualitatively improves outcomes in less than 18 months: a prospective cohort study in a large metropolitan centre
Authors: Phan Vinh-An Huu , van Langenberg Daniel R , Grafton Rachel , Andrews Jane M 
Published: May 2012

IntroductionMaintaining high efficacy and quality of care in inflammatory bowel disease (IBD) management is a priority. The authors examined whether the introduction of a formal IBD Service (IBDS) positively influenced outcomes for their patients.MethodsIn 2007-2008, all IBD patients attending the Royal Adelaide Hospital were surveyed regarding clinical/demographic data, IBD knowledge, quality of life, mental health and satisfaction. Survey responders were re-surveyed ≥15 months later.Results162 responded to survey 1 and 81 again responded to survey 2. Within the responders, 61% had Crohn's disease and 48% were men. Compared with survey 1, the proportions of patients with improved knowledge, adherence, satisfaction with care, QoL (≥5 points), anxiety and depression scores were 63% (95% CI 51 to 73), 62% (95% CI 50 to 72), 65% (95% CI 54 to 76), 42% (95% CI 31 to 54), 52% (95% CI 40 to 63) and 43% (95% CI 32 to 55), respectively. When comparing survey 2 with survey 1, reductions in hospitalisation (48% vs 30%, p=0.02), courses of corticosteroids and opiates (mean 1.63 vs 0.91 and 1.00 vs 0.61, both p<0.05) and overall medications (5.63 vs 4.65, p<0.05), were seen. Fewer 2009 non-responders required hospitalisation (53% vs 21%, p<0.001), suggesting a `cohort' rather than `responder-specific' effect.ConclusionsThe introduction of an IBDS resulted in improved patient outcomes with significant reductions in negative markers for IBD morbidity including: hospitalisations, polypharmacy, steroid and opiate use. Despite increased costs in additional staff, these measures are likely to be cost effective.
The ERCP quality network benchmarking project: a preliminary comparison of practice in UK and USA
Authors: Oppong Kofi W , Romagnuolo Joseph , Cotton Peter B 
Published: May 2012

ObjectiveThe Endoscopic retrograde cholangiopancreatography (ERCP) Quality Network is a voluntary system for submission of data to generate individual report cards and benchmarking. The aim of this study was to compare aspects of ERCP practice between USA and UK participants.DesignAnalysis was limited to USA and UK based endoscopists who had each entered more than 30 cases. A number of practice and performance measures were studied including, rates of deep biliary cannulation, sedation use and success in bile duct stone removal.Setting and patientsPatients attending for routine and emergency ERCP in participating tertiary and secondary care units in the UK and USA.Results61 US endoscopists performed 18 182 procedures and 16 UK endoscopists 3172, respectively. The UK participants performed less complex procedures as judged by the accepted complexity grading system, 8% versus 35% at grade 3, p<0.001. There was a significantly greater use of sedation as opposed to anaesthesia in the UK 97% versus 34%, p<0.001. UK deep biliary cannulation rate was 93% versus 97%, p<0.001. For small bile duct stones (<10 mm) the UK success rate was 96% compared with 99%, p<0.001.ConclusionThe present data, while not purporting to be an accurate representation of practice in either country, documents good technical success in both cohorts, albeit significantly better in the USA. The inexorable drive to greater accountability and transparency of outcomes in endoscopic practice is likely to lead to increased participation in subsequent benchmarking projects.
ONYX versus n-BCA for embolization of cranial dural arteriovenous fistulas
Authors: Rabinov James David , Yoo Albert J , Ogilvy Christopher S , Carter Bob S , Hirsch Joshua A 
Published: May 2012

PurposeTo evaluate the efficacy of n-butyl-2-cyanoacrylate (Trufill n-BCA) versus ethylene vinyl alcohol copolymer (ONYX) for the embolization of cranial dural arteriovenous fistulas (DAVF).MethodsFifty-three consecutive patients with cranial dural AVF were treated with liquid embolic agents from November, 2003 to November, 2008. These 53 patients had 56 lesions treated with arterial embolization. Patients embolized to completion underwent follow-up angiography at 3 months to assess for durable occlusion.ResultsTwenty-one lesions were treated with n-BCA. Seven patients treated with n-BCA had initial angiographic occlusion of their DAVF, which were durable at 3 months. Six patients had adjunctive treatment with coils and/or polyvinyl alcohol particles, but none of these were occluded by endovascular treatment alone. Eleven patients underwent post-embolization surgery for closure of their DAVF. There was one death related to intractable status epilepticus at presentation. One patient developed a major stroke from venous sinus thrombosis after embolization. Thirty-five lesions were treated with ONYX in 34 patients. Twenty-nine patients treated with ONYX had initial angiographic occlusion of their DAVF by embolization alone. One patient had recurrence at 3 months and was re-treated out of 27 total follow-ups. Four patients underwent post-embolization surgical obliteration of their lesions. No deaths or major strokes occurred in this cohort.ConclusionInitial angiographic occlusion (p=0.0004) and durable angiographic occlusion (p=0.0018) rates for embolization of cranial DAVF show a statistically significant higher efficacy with ONYX compared with n-BCA. Patients embolized with ONYX underwent surgery less frequently compared with those treated with n-BCA (p=0.0015).
Polarized continuum model study of bond dissociation energies of the O–NO2 bond — A density functional theory study and natural bond order analysis
Authors: Ruizhou Zhang , Zhumu Fu , Xiaohong Li , Xianzhou Zhang 
Published: May 2012

Density functional methods (B3LYP, B3PW91, B3P86, and MPWB95) with 6–31G** basis sets and complete basis methods are employed to investigate the bond dissociation energies (BDEs) of the O–NO2 bond for seven O-nitroalcohol compounds in acetonitrile solution. B3LYP/6–31+G**, (RO)B3LYP/6–311++G(2df,2p), and B3LYP/6–311G(d,p) methods are also used. By comparing the calculated results with the experimental values, B3LYP/6–31+G** is the most accurate method to compute the reliable BDEs for the studied compounds. The substituent effects on the O–NO2 BDEs are analyzed. It is found that electron-withdrawing groups increase the BDE of the parent compound, whereas electron-donating groups decrease the BDE of the parent compound. Further, the natural bond orbital analysis shows that there exist good linear correlations between E(2) and Hammett constants, the BDE, and the difference of the second-order stabilization energies E(2) of lpO3 → BD*(O1–N1) and lpO3 → BD*(O2–N1).
Factors governing the regulation ofSclerotinia sclerotiorumcutinase A and polygalacturonase 1 during different stages of infection
Authors: Bashi Zafer Dallal , Rimmer S. Roger , Khachatourians George G. , Hegedus Dwayne D. 
Published: May 2012

Sclerotinia sclerotiorum releases hydrolytic enzymes that sequentially degrade the plant cuticle, middle lamellae, and primary and secondary cell walls. The cuticle was found to be a barrier to S. sclerotiorum infection, as leaves stripped of epicuticular wax were more rapidly colonized. Consequently, the factors affecting the regulation of genes encoding polygalacturonase 1 (SsPG1) and a newly identified cutinase (SsCUTA) were examined. In vitro, SsCutA transcripts were detected within 1 h postinoculation of leaves, and expression was primarily governed by contact of mycelia with solid surfaces. Expression of SsPg1 was moderately induced by contact with solid surfaces including the leaf, and expression was restricted to the expanding margin of the lesion as the infection progressed. SsPg1 expression was induced by carbohydrate starvation but repressed by galacturonic acid. Glucose supported a basal level of SsPg1 expression but accentuated expression when provided to mycelia used to inoculate leaves. These observations were contrary to earlier reports indicating that glucose repressed SsPg1 expression while galacturonic acid induced expression. Pharmacological studies showed that disruption of calcium signalling affected SsCutA and SsPg1 expression and decreased S. sclerotiorum virulence, whereas elevated cAMP levels reduced virulence without affecting gene expression. The mechanisms involved in coordinating the expression of S. sclerotiorum hydrolytic enzymes throughout the various stages of the infection are discussed.
Bacterial contamination of tile drainage water and shallow groundwater under different application methods of liquid swine manure
Authors: Samarajeewa A.D. , Glasauer S.M. , Lauzon J.D. , O’Halloran I.P. , Parkin Gary W. , Dunfield K.E. 
Published: May 2012

A 2 year field experiment evaluated liquid manure application methods on the movement of manure-borne pathogens ( Salmonella sp.) and indicator bacteria ( Escherichia coli and Clostridium perfringens ) to subsurface water. A combination of application methods including surface application, pre-application tillage, and post-application incorporation were applied in a randomized complete block design on an instrumented field site in spring 2007 and 2008. Tile and shallow groundwater were sampled immediately after manure application and after rainfall events. Bacterial enumeration from water samples showed that the surface-applied manure resulted in the highest concentration of E. coli in tile drainage water. Pre-tillage significantly (p < 0.05) reduced the movement of manure-based E. coli and C. perfringens to tile water and to shallow groundwater within 3 days after manure application (DAM) in 2008 and within 10 DAM in 2007. Pre-tillage also decreased the occurrence of Salmonella sp. in tile water samples. Indicator bacteria and pathogens reached nondetectable levels within 50 DAM. The results suggest that tillage before application of liquid swine manure can minimize the movement of bacteria to tile and groundwater, but is effective only for the drainage events immediately after manure application or initial rainfall-associated drainage flows. Furthermore, the study highlights the strong association between bacterial concentrations in subsurface waters and rainfall timing and volume after manure application.
Introducing an interface between FeynRules and WHIZARD
Authors: Christensen Neil D. , Duhr Claude , Fuks Benjamin , Reuter Jürgen , Speckner Christian 
Published: May 2012

AbstractWhile Monte Carlo event generators like Whizard have become indispensable tools in studying the impact of new physics on collider observables over the last decades, the implementation of new models in such packages has remained a rather awkward and error-prone process. Recently, the FeynRules package was introduced which greatly simplifies this process by providing a single unified model format from which model implementations for many different Monte Carlo codes can be derived automatically. In this note, we present an interface which extends FeynRules to provide this functionality also for the Whizard package, thus making Whizard’s strengths and performance easily available to model builders.
MEK Inhibition Leads to PI3K/AKT Activation by Relieving a Negative Feedback on ERBB Receptors
Authors: Turke Alexa B. , Song Youngchul , Costa Carlotta , Cook Rebecca , Arteaga Carlos L. , Asara John M. , Engelman Jeffrey A. 
Published: May 2012

Abstract
The phosphoinositide 3-kinase (PI3K)/AKT and RAF/MEK/ERK signaling pathways are activated in a wide range of human cancers. In many cases, concomitant inhibition of both pathways is necessary to block proliferation and induce cell death and tumor shrinkage. Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway, thereby decreasing the effectiveness of single-agent targeted therapies. In this study, we describe a feedback mechanism in which MEK inhibition leads to activation of PI3K/AKT signaling in EGFR and HER2-driven cancers. We found that MEK inhibitor–induced activation of PI3K/AKT resulted from hyperactivation of ERBB3 as a result of the loss of an inhibitory threonine phosphorylation in the conserved juxtamembrane domains of EGFR and HER2. Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway, which was no longer responsive to MEK inhibition. Taken together, these results elucidate an important, dominant feedback network regulating central oncogenic pathways in human cancer. Cancer Res; 72(13); 3228–37. ©2012 AACR.
Abstract A18: Molecular mechanisms of nuclear receptor-dependent chromosomal translocations
Authors: Yang Liuqing 
Published: May 2012

Abstract
Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear widespread in solid tumors, but the underlying molecular basis has remained elusive. By establishing a cellular model to dissect specific and inducible translocations in the absence of proliferative selection, we report an androgen receptor (AR)-dependent pathway for tumor translocation events in prostate cancer cells. This pathway is initiated by binding of liganded AR to specific intronic sites that triggers intra- and inter-chromosomal interactions that place translocation sites in close spatial proximity, and local architectural alterations that permit serial recruitment of an enzymatic machinery, including Activation-Induced Cytidine Deaminase (AID) induced by liganded AR and genotoxic stress. Strikingly, this process is enhanced by the expression of the ORF2 endonuclease from LINE-1 repeats, caused by diminished PIWIL1 and increased AID, generating staggered double-strand breaks (DSBs) at intronic AR binding sites that result in tumor translocation by components of the Non-Homologous Ending Joining (NHEJ) mechanism. Together, these findings reveal specific architectural/enzymatic mechanisms underlying well-defined chromosomal translocations observed in tumors, which may function in many types of tumors and in other biological and pathological processes.
Citation Information: Cancer Res 2009;69(23 Suppl):A18.