bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions
Authors: Rathinakumar Ramesh , Dutta Moumita , Zhu Ping , Johnson Welkin E. , Roux Kenneth H. 
Published: November 2011

ABSTRACT
The broadly neutralizing monoclonal antibodies (MAbs) 4E10, 2F5, and Z13e1 target membrane-proximal external region (MPER) epitopes of HIV-1 gp41 in a manner that remains controversial. The requirements for initial lipid bilayer binding and/or CD4 ligation have been proposed. To further investigate these issues, we probed for binding of these MAbs to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) virions with protein A-conjugated gold (PAG) nanoparticles using negative-stain electron microscopy. We found moderate levels of PAG associated with unliganded HIV-1 and SIV virions incubated with the three MAbs. Significantly higher levels of PAG were associated with CD4-liganded HIV-1 (epitope-positive) but not SIV (epitope-negative) virions. A chimeric SIV virion displaying the HIV-1 4E10 epitope also showed significantly higher PAG association after CD4 ligation and incubation with 4E10. MAbs accumulated rapidly on CD4-liganded virions and slowly on unliganded virions, although both reached similar levels in time. Anti-MPER epitope-specific binding was stable to washout. Virions incubated with an irrelevant MAb or CD4-only (no MAb) showed negligible PAG association, as did a vesicle-rich fraction devoid of virions. Preincubation with Fab 4E10 inhibited both specific and nonspecific 4E10 IgG binding. Our data provide evidence for moderate association of anti-MPER MAbs to viral surfaces but not lipid vesicles, even in the absence of cognate epitopes. Significantly greater MAb interaction occurs in epitope-positive virions following long incubation or CD4 ligation. These findings are consistent with a two-stage binding model where these anti-MPER MAbs bind first to the viral lipid bilayer and then to the MPER epitopes following spontaneous or induced exposure.
Significant Association of Multiple Human Cytomegalovirus Genomic Loci with Glioblastoma Multiforme Samples
Authors: Ranganathan Padhma , Clark Paul A. , Kuo John S. , Salamat M. Shahriar , Kalejta Robert F. 
Published: November 2011

ABSTRACT
Viruses are appreciated as etiological agents of certain human tumors, but the number of different cancer types induced or exacerbated by viral infections is unknown. Glioblastoma multiforme (GBM)/astrocytoma grade IV is a malignant and lethal brain cancer of unknown origin. Over the past decade, several studies have searched for the presence of a prominent herpesvirus, human cytomegalovirus (HCMV), in GBM samples. While some have detected HCMV DNA, RNA, and proteins in GBM tissues, others have not. Therefore, any purported association of HCMV with GBM remains controversial. In most of the previous studies, only one or a select few viral targets were analyzed. Thus, it remains unclear the extent to which the entire viral genome was present when detected. Here we report the results of a survey of GBM specimens for as many as 20 different regions of the HCMV genome. Our findings indicate that multiple HCMV loci are statistically more likely to be found in GBM samples than in other brain tumors or epileptic brain specimens and that the viral genome was more often detected in frozen samples than in paraffin-embedded archival tissue samples. Finally, our experimental results indicate that cellular genomes substantially outnumber viral genomes in HCMV-positive GBM specimens, likely indicating that only a minority of the cells found in such samples harbor viral DNA. These data argue for the association of HCMV with GBM, defining the virus as oncoaccessory. Furthermore, they imply that, were HCMV to enhance the growth or survival of a tumor (i.e., if it is oncomodulatory), it would likely do so through mechanisms distinct from classic tumor viruses that express transforming viral oncoproteins in the overwhelming majority of tumor cells.
Naturally Occurring Fragments from Two Distinct Regions of the Prostatic Acid Phosphatase Form Amyloidogenic Enhancers of HIV Infection
Authors: Arnold Franziska , Schnell Jacqueline , Zirafi Onofrio , Stürzel Christina , Meier Christoph , Weil Tanja , Ständker Ludger , Forssmann Wolf-Georg , Roan Nadia R. , Greene Warner C. , Kirchhoff Frank , Münch Jan 
Published: November 2011

ABSTRACT
Semen is the major vector for HIV-1 transmission. We previously isolated C-proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission.
Genetic Informational RNA Is Not Required for Recombinant Prion Infectivity
Authors: Wang Fei , Zhang Zhihong , Wang Xinhe , Li Jiali , Zha Liang , Yuan Chong-Gang , Weissmann Charles , Ma Jiyan 
Published: November 2011

ABSTRACT
Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and synthetic phospholipid 1-palmitoyl-2-oleoylphosphatidylglycerol is competent to infect cultured cells and cause prion disease in wild-type mice. Our results show that genetic informational RNA is not required for recombinant prion infectivity.
Innate Sensing of Foamy Viruses by Human Hematopoietic Cells
Authors: Rua Réjane , Lepelley Alice , Gessain Antoine , Schwartz Olivier 
Published: November 2011

ABSTRACT

Foamy viruses (FV) are nonpathogenic retroviruses that have cospeciated with primates for millions of years. FV can be transmitted through severe bites from monkeys to humans. Viral loads remain generally low in infected humans, and no secondary transmission has been reported. Very little is known about the ability of FV to trigger an innate immune response in human cells. A few previous reports suggested that FV do not induce type I interferon (IFN) in nonhematopoietic cells. Here, we examined how human hematopoietic cells sense FV particles and FV-infected cells. We show that peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 detect FV, produce high levels of type I IFN, and express the IFN-stimulated gene MxA. Fewer than 20 FV-infected cells are sufficient to trigger an IFN response. Both prototypic and primary viruses stimulated IFN release. Donor cells expressing a replication-defective virus, carrying a mutated reverse transcriptase, induced IFN production by target cells as potently as wild-type virus. In contrast, an FV strain with
env
deleted, which does not produce viral particles, was inactive. IFN production was blocked by an inhibitor of endosomal acidification (bafilomycin A1) and by an endosomal Toll-like receptor (TLR) antagonist (A151). Silencing experiments in Gen2.2 further demonstrated that TLR7 is involved in FV recognition. Therefore, FV are potent inducers of type I IFN by pDCs and by PBMCs. This previously underestimated activation of the innate immune response may be involved in the control of viral replication in humans.
Dynamic Chromatin Environment of Key Lytic Cycle Regulatory Regions of the Epstein-Barr Virus Genome
Authors: Ramasubramanyan Sharada , Osborn Kay , Flower Kirsty , Sinclair Alison J. 
Published: November 2011

ABSTRACTThe ability of Epstein-Barr virus (EBV) to establish latency allows it to evade the immune system and to persist for the lifetime of its host; one distinguishing characteristic is the lack of transcription of the majority of viral genes. Entry into the lytic cycle is coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and EB1), and downstream effectors, while viral genome replication requires the concerted action of Zta and six other viral proteins at the origins of lytic replication. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1,BRLF1,BMRF1, andBALF5) and the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin-like environment (trimethylation of histone H3 at lysine 9 [H3K9me3] and lysine 27 [H3K27me3]), which blocks the interaction of some transcription factors with DNA, encompasses the key early lytic regulatory regions. Epigenetic silencing of the EBV genome is also imposed by DNA methylation during latency. The chromatin environment changes during the lytic cycle with activation of histones H3, H4, and H2AX occurring at both the origins of replication and at the key lytic regulatory elements. We propose that Zta is able to reverse the effects of latency-associated repressive chromatin at EBV early lytic promoters by interacting with Zta response elements within the H3K9me3-associated chromatin and demonstrate that these interactions occurin vivo. Since the interaction of Zta with DNA is not inhibited by DNA methylation, it is clear that Zta uses two routes to overcome epigenetic silencing of its genome.
Marked Endotheliotropism of Highly Pathogenic Avian Influenza Virus H5N1 following Intestinal Inoculation in Cats
Authors: Reperant Leslie A. , van de Bildt Marco W. G. , van Amerongen Geert , Leijten Lonneke M. E. , Watson Simon , Palser Anne , Kellam Paul , Eissens Anko C. , Frijlink Hendrik W. , Osterhaus Albert D. M. E. , Kuiken Thijs 
Published: November 2011

ABSTRACT
Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since influenza viruses typically infect mammals via the respiratory tract. The dissemination of HPAIV H5N1 following intestinal entry and associated pathogenesis are largely unknown. To assess the route of spread of HPAIV H5N1 to other organs and to determine its associated pathogenesis, we inoculated infected chicken liver homogenate directly into the intestine of cats by use of enteric-coated capsules. Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease. The spread of HPAIV H5N1 from the lumen of the intestine to other organs took place via the blood and lymphatic vascular systems but not via neuronal transmission. Remarkably, the systemic spread of the virus via the vascular system was associated with massive infection of endothelial and lymphendothelial cells, resulting in widespread hemorrhages. This is unique for influenza in mammals and resembles the pathogenesis of HPAIV infection in terrestrial poultry. It contrasts with the pathogenesis of systemic disease from the same virus following entry via the respiratory tract, where lesions are characterized mainly by necrosis and inflammation and are associated with the presence of influenza virus antigen in parenchymal, not endothelial cells. The marked endotheliotropism of the virus following intestinal inoculation indicates that the pathogenesis of systemic influenza virus infection in mammals may differ according to the portal of entry.
Melanoma Differentiation-Associated Gene 5 Is Critical for Protection against Theiler's Virus-Induced Demyelinating Disease
Authors: Jin Young-Hee , Kim Seung Jae , So Eui Young , Meng Liping , Colonna Marco , Kim Byung S. 
Published: November 2011

ABSTRACTInfection of dendritic and glial cells with Theiler's murine encephalomyelitis virus (TMEV) induces various cytokines via Toll-like receptor- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways. However, the involvement and role of MDA5 in cytokine gene activation and the pathogenesis of TMEV-induced demyelinating disease are largely unknown. In this study, we demonstrate that MDA5 plays a critical role in the production of TMEV-induced alpha interferon (IFN-α) during early viral infection and in protection against the development of virus-induced demyelinating disease. Our results indicate that MDA5-deficient 129SvJ mice display significantly higher viral loads and apparent demyelinating lesions in the central nerve system (CNS) accompanied by clinical symptoms compared with wild-type 129SvJ mice. During acute viral infection, MDA5-deficient mice produced elevated levels of chemokines, consistent with increased cellular infiltration, but reduced levels of IFN-α, known to control T cell responses and cellular infiltration. Additional studies with isolated CNS glial cells from these mice suggest that cells from MDA5-deficient mice are severely compromised in the production of IFN-α upon viral infection, which results in increased cellular infiltration and viral loads in the CNS. Despite inadequate stimulation, the overall T cell responses to the viral determinants were significantly elevated in MDA5-deficient mice, reflecting the increased cellular infiltration. Therefore, the lack of MDA5-mediated IFN-α production may facilitate a massive viral load and elevated cellular infiltration in the CNS during early viral infection, leading to the pathogenesis of demyelinating disease.
A systematic review of patient-reported outcome measures used to assess Achilles tendon rupture management: What's being used and should we be using it?
Authors: Kearney Rebecca S , Achten Juul , Lamb Sarah E , Plant Caroline , Costa Matthew L 
Published: November 2011

BackgroundCurrently, there is no consensus regarding the optimal management for patients following an Achilles tendon rupture. To allow comparisons between different treatments, a universally accepted outcome measure is required. However, there are currently a range of these reported within the literature.ObjectiveTo recommend the most suitable patient-reported outcome measure for the assessment of patients following an Achilles tendon rupture, based on a systematic review of first what is currently used and second evidence of validity.MethodsThe electronic databases MEDLINE, EMBASE and AMED were searched up to September 2010. Predefined inclusion and exclusion criteria were applied to identify what outcome measures are reported in the literature. Aspects of validity were defined and a checklist used to determine which aspects have been evaluated.ResultsTwenty-one outcome measures in 50 research papers were identified. The most commonly used was the American Orthopaedic Foot and Ankle Society hind-foot score. Of the 21 outcome measures, only 4 cited independent validation data. Of these four, only the ‘Achilles tendon Total Rupture Score’ reported evidence to support multiple facets of validity, as defined by a predetermined criteria checklist.ConclusionsThe Achilles tendon Total Rupture Score was identified as the only outcome measure which has demonstrated multiple facets of validity for use in this patient group. However, even this tool has limitations. Researchers should be aware of the limitations of the available outcome measurement tools and check on their validity before use in clinical research.
Calculating anisotropic physical properties from texture data using the MTEX open-source package
Authors: Mainprice David , Hielscher Ralf , Schaeben Helmut 
Published: November 2011

Abstract
This paper presents the background for the calculation of physical properties of an aggregate from constituent crystal properties and the texture of the aggregate in a coherent manner. Emphasis is placed on the important tensor properties of 2nd and 4th rank with applications in rock deformation, structural geology, geodynamics and geophysics. We cover texture information that comes from pole figure diffraction and single orientation measurements (electron backscattered diffraction or EBSD, electron channelling pattern, Laue pattern, optical microscope universal-stage). In particular, we provide explicit formulae for the calculation of the averaged tensor from individual orientations or from an orientation distribution function (ODF). For the latter we consider numerical integration and an approach based on the expansion into spherical harmonics. This paper also serves as a reference paper for the mathematical tensor capabilities of the texture analysis software MTEX, which is a comprehensive, freely available MatLab toolbox that covers a wide range of problems in quantitative texture analysis, for example, ODF modelling, pole figure to ODF inversion, EBSD data analysis and grain detection. MTEX offers a programming interface which allows the processing of involved research problems as well as highly customizable visualization capabilities; MTEX is therefore ideal for presentations, publications and teaching demonstrations.
Diversity of Human Leukemia Xenograft Mouse Models: Implications for Disease Biology
Authors: Meyer Lüder Hinrich , Debatin Klaus-Michael 
Published: November 2011

AbstractOver the past decade, xenografting human leukemia cells into mice with different levels of immunodeficiency, with or without preconditioning, has provided an important tool to study various aspects of leukemia biology and to identify distinct clinical risk groups for evaluation of novel therapeutic strategies, as well as the possibility of amplifying human leukemia cells in vivo. Interestingly, these models using human acute lymphoblastic leukemia and acute myeloid leukemia cells as xenografts recapitulate many clinical features of the disease. Similar to the human environment (for example, in the bone marrow), transplanted leukemia cells in the murine setting are exposed to both favorable and unfavorable conditions for engraftment that may exert a distinct pressure for selection of subclones. Thus, results obtained in these models may vary depending on the experimental setup. The impact of in vivo growth of human leukemia cells on the background of a more or less hostile murine environment for leukemia biology and the course of the disease in patients are discussed in the context of the diversity of xenograft models. Cancer Res; 71(23); 7141–4. ©2011 AACR.
Anti-EGFR Antibody Cetuximab Enhances the Cytolytic Activity of Natural Killer Cells toward Osteosarcoma
Authors: Pahl Jens H.W. , Ruslan S. Eriaty N. , Buddingh Emilie P. , Santos Susy J. , Szuhai Karoly , Serra Massimo , Gelderblom Hans , Hogendoorn Pancras C.W. , Egeler R. Maarten , Schilham Marco W. , Lankester Arjan C. 
Published: November 2011

Abstract
Purpose: Osteosarcoma and Ewing's sarcoma are the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease have a poor prognosis, illustrating the need for alternative therapies. Sarcoma cells are susceptible to the cytolytic activity of resting natural killer (NK) cells which can be improved by interleukin (IL)-15 stimulation. In this study, we explored whether the cytolytic function of resting NK cells can be augmented and specifically directed toward sarcoma cells by antibody-dependent cellular cytotoxicity (ADCC).
Experimental Design: Epidermal growth factor receptor (EGFR) expression was examined on osteosarcoma and Ewing's sarcoma cell lines by flow cytometry and in osteosarcoma biopsy and resection specimens by immunohistochemistry. Cetuximab-mediated ADCC by NK cells from osteosarcoma patients and healthy controls was measured with 4-hour 51Cr release assays.
Results: EGFR surface expression was shown on chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cells (12/12), most primary osteosarcoma cultures (4/5), and few Ewing's sarcoma cell lines (2/7). In the presence of cetuximab, the cytolytic activity of resting NK cells against all EGFR-expressing sarcoma cells was substantially increased and comparable with that of IL-15–activated NK cells. Surface EGFR expression on primary osteosarcoma cultures correlated with EGFR expression in the original tumor. The cytolytic activity of osteosarcoma patient-derived NK cells against autologous tumor cells was as efficient as that of NK cells from healthy donors.
Conclusion: Our data show that the cytolytic potential of resting NK cells can be potentiated and directed toward osteosarcoma cells with cetuximab. Therefore, cetuximab-mediated immunotherapy may be considered a novel treatment modality in the management of advanced osteosarcoma. Clin Cancer Res; 18(2); 432–41. ©2011 AACR.
Colchicine Reduces Postoperative Atrial Fibrillation
Authors: Imazio Massimo , Brucato Antonio , Ferrazzi Paolo , Rovere Maria Elena , Gandino Anna , Cemin Roberto , Ferrua Stefania , Belli Riccardo , Maestroni Silvia , Simon Caterina , Zingarelli Edoardo , Barosi Alberto , Sansone Fabrizio , Patrini Davide , Vitali Ettore , Trinchero Rita , Spodick David H. , Adler Yehuda ,   for the COPPS Investigators
Published: November 2011

Background—
Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery.

Methods and Results—

The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively;
P
=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days;
P
=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days;
P
=0.009). Side effects were similar in the study groups.

Conclusion—
Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
.
Unique identifier: NCT00128427.
Intrinsic Adaptation in Autonomous Recurrent Neural Networks
Authors: Marković Dimitrije , Gros Claudius 
Published: November 2011

A massively recurrent neural network responds on one side to input stimuli and is autonomously active, on the other side, in the absence of sensory inputs. Stimuli and information processing depend crucially on the qualia of the autonomous-state dynamics of the ongoing neural activity. This default neural activity may be dynamically structured in time and space, showing regular, synchronized, bursting, or chaotic activity patterns. We study the influence of nonsynaptic plasticity on the default dynamical state of recurrent neural networks. The nonsynaptic adaption considered acts on intrinsic neural parameters, such as the threshold and the gain, and is driven by the optimization of the information entropy. We observe, in the presence of the intrinsic adaptation processes, three distinct and globally attracting dynamical regimes: a regular synchronized, an overall chaotic, and an intermittent bursting regime. The intermittent bursting regime is characterized by intervals of regular flows, which are quite insensitive to external stimuli, interceded by chaotic bursts that respond sensitively to input signals. We discuss these findings in the context of self-organized information processing and critical brain dynamics.