bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses
Authors: Liu Wen-Chun , Lin Chia-Ying , Tsou Yung-Ta , Jan Jia-Tsrong , Wu Suh-Chin 
Published: May 2015

ABSTRACT
Neuraminidase (NA), an influenza virus envelope glycoprotein, removes sialic acid from receptors for virus release from infected cells. For this study, we used a baculovirus-insect cell expression system to construct and purify recombinant NA (rNA) proteins of H5N1 (A/Vietnam/1203/2004) and pandemic H1N1 (pH1N1) (A/Texas/05/2009) influenza viruses. BALB/c mice immunized with these proteins had high titers of NA-specific IgG and NA-inhibiting (NI) antibodies against H5N1, pH1N1, H3N2, and H7N9 viruses. H5N1 rNA immunization resulted in higher quantities of NA-specific antibody-secreting B cells against H5N1 and heterologous pH1N1 viruses in the spleen. H5N1 rNA and pH1N1 rNA immunizations both provided complete protection against homologous virus challenges, with H5N1 rNA immunization providing better protection against pH1N1 virus challenges. Cross-reactive NI antibodies were further dissected via pH1N1 rNA protein immunizations with I149V (NA with a change of Ile to Val at position 149), N344Y, and I365T/S366N NA mutations. The I365T/S366N mutation of pH1N1 rNA enhanced cross-reactive NI antibodies against H5N1, H3N2, and H7N9 viruses. It is our hope that these findings provide useful information for the development of an NA-based universal influenza vaccine.

IMPORTANCE
Neuraminidase (NA) is an influenza virus enzymatic protein that cleaves sialic acid linkages on infected cell surfaces, thus facilitating viral release and contributing to viral transmission and mucus infection. In currently available inactivated or live, attenuated influenza vaccines based on the antigenic content of hemagglutinin proteins, vaccine efficacy can be contributed partly through NA-elicited immune responses. We investigated the NA immunity of different recombinant NA (rNA) proteins associated with pH1N1 and H5N1 viruses. Our results indicate that H5N1 rNA immunization induced more potent cross-protective immunity than pH1N1 rNA immunization, and three mutated residues, I149V, I365T, and S366N, near the NA enzyme active site(s) are linked to enhanced cross-reactive NA-inhibiting antibodies against heterologous and heterosubtypic influenza A viruses. These findings provide useful information for the development of an NA-based universal influenza vaccine.
Interferon Gamma Prolongs Survival of Varicella-Zoster Virus-Infected Human NeuronsIn Vitro
Authors: Baird Nicholas L. , Bowlin Jacqueline L. , Hotz Taylor J. , Cohrs Randall J. , Gilden Don 
Published: May 2015

ABSTRACTInfection of human neuronsin vitrowith varicella-zoster virus (VZV) at a low multiplicity of infection does not result in a cytopathic effect (CPE) within 14 days postinfection (dpi), despite production of infectious virus. We showed that by 28 dpi a CPE ultimately developed in infected neurons and that interferon gamma inhibited not only the CPE but also VZV DNA accumulation, transcription, and virus production, thereby prolonging the life of VZV-infected neurons.
Novel Functions of Hendra Virus G N-Glycans and Comparisons to Nipah Virus
Authors: Bradel-Tretheway Birgit G. , Liu Qian , Stone Jacquelyn A. , McInally Samantha , Aguilar Hector C. 
Published: May 2015

ABSTRACT

Hendra virus (HeV) and Nipah virus (NiV) are reportedly the most deadly pathogens within the
Paramyxoviridae
family. These two viruses bind the cellular entry receptors ephrin B2 and/or ephrin B3 via the viral attachment glycoprotein G, and the concerted efforts of G and the viral fusion glycoprotein F result in membrane fusion. Membrane fusion is essential for viral entry into host cells and for cell-cell fusion, a hallmark of the disease pathobiology. HeV G is heavily N-glycosylated, but the functions of the N-glycans remain unknown. We disrupted eight predicted N-glycosylation sites in HeV G by conservative mutations (Asn to Gln) and found that six out of eight sites were actually glycosylated (G2 to G7); one in the stalk (G2) and five in the globular head domain (G3 to G7). We then tested the roles of individual and combined HeV G N-glycan mutants and found functions in the modulation of shielding against neutralizing antibodies, intracellular transport, G-F interactions, cell-cell fusion, and viral entry. Between the highly conserved HeV and NiV G glycoproteins, similar trends in the effects of N-glycans on protein functions were observed, with differences in the levels at which some N-glycan mutants affected such functions. While the N-glycan in the stalk domain (G2) had roles that were highly conserved between HeV and NiV G, individual N-glycans in the head affected the levels of several protein functions differently. Our findings are discussed in the context of their contributions to our understanding of HeV and NiV pathogenesis and immune responses.

IMPORTANCE
Viral envelope glycoproteins are important for viral pathogenicity and immune evasion. N-glycan shielding is one mechanism by which immune evasion can be achieved. In paramyxoviruses, viral attachment and membrane fusion are governed by the close interaction of the attachment proteins H/HN/G and the fusion protein F. In this study, we show that the attachment glycoprotein G of Hendra virus (HeV), a deadly paramyxovirus, is N-glycosylated at six sites (G2 to G7) and that most of these sites have important roles in viral entry, cell-cell fusion, G-F interactions, G oligomerization, and immune evasion. Overall, we found that the N-glycan in the stalk domain (G2) had roles that were very conserved between HeV G and the closely related Nipah virus G, whereas individual N-glycans in the head quantitatively modulated several protein functions differently between the two viruses.
MAVS Coordination of Antiviral Innate Immunity
Authors: Vazquez Christine , Horner Stacy M. 
Published: May 2015

ABSTRACT
RNA virus infection is sensed in the cytoplasm by the retinoic acid-inducible gene I (RIG-I)-like receptors. These proteins signal through the host adaptor protein MAVS to trigger the antiviral innate immune response. Here, we describe how MAVS subcellular localization impacts its function and the regulation underlying MAVS signaling. We propose a model to describe how the coordination of MAVS functions at the interface between the mitochondria and the mitochondrion-associated endoplasmic reticulum (ER) membrane programs antiviral signaling.
Ecological Drivers of Virus Evolution: Astrovirus as a Case Study
Authors: Mendenhall Ian H. , Smith Gavin J. D. , Vijaykrishna Dhanasekaran 
Published: May 2015

ABSTRACT
Although RNA viruses exhibit a high frequency of host jumps, major differences exist among the different virus families. Astroviruses infect a wide range of hosts, affecting both public health systems and economic production chains. Here we delineate the ecological and adaptive processes that drive the cross-species transmission of astroviruses. We observe that distinct transmission zones determine the prevailing astrovirus host and virus diversity, which in turn suggests that no single host group (e.g., bats) can be the natural reservoir, as illustrated through our phylogenetic analysis.
Interventions for migraine prophylaxis: protocol of an umbrella systematic review and network meta-analysis
Authors: Zheng Hui , Chen Min , Huang Dequan , Li Juan , Chen Qin , Fang Jianqiao 
Published: May 2015

IntroductionMultiple interventions are effective for migraine prophylaxis. However, the comparative effectiveness of these interventions is still not clear. Therefore, the aim of this study is to summarise the direct and indirect evidence for pharmacological and non-pharmacological interventions to prevent migraine attack.Methods and analysisWe will perform an umbrella systematic review to identify eligible randomised controlled trials (RCTs) for the recommended interventions for migraine prophylaxis according to the guidelines. A comprehensive literature search will be conducted in MEDLINE, EMBASE and the Cochrane library for systematic reviews, which will be screened for RCTs. We will describe the general information of the RCTs for participants, interventions, outcome measurements, comparisons and the primary findings. Additionally, a network meta-analysis will be conducted to determine the comparative effectiveness of the treatments with a random-effects model. The absolute and relative effectiveness of the treatments will be provided. The heterogeneity and inconsistency between trials will be assessed by the I2statistical test and Cochrane's Q test. Risk of bias will be assessed and the overall strength of the evidence will be summarised.DiscussionThe result of this network meta-analysis will provide direct and indirect evidence of treatments for migraine prophylaxis, and it may provide a ranking of the treatments for patients and clinicians to help them select the best option.Trial registration numberPROSPERO CRD42015015297.
Characterising ‘near miss’ events in complex laparoscopic surgery through video analysis
Authors: Bonrath Esther M , Gordon Lauren E , Grantcharov Teodor P 
Published: May 2015

BackgroundRoot cause analyses of surgical complications are of high importance to ensure surgical quality, but specific details on technical causes often remain unclear. Identifying subclinical intraoperative incidents attributable to technical errors is essential for developing rescue mechanisms to prevent adverse outcomes.ObjectiveDescriptive study to characterise intraoperative technical error-event patterns in successful laparoscopic procedures.MethodsEvents (injuries) identified during prior blinded analyses of 54 unedited recordings of bariatric laparoscopic procedures were subjected to a secondary review to determine the presumed underlying error mechanism. The recordings were obtained from one university-based bariatric collaborative programme, and represented consultant, fellow and shared trainee cases.ResultsSixty-six events were identified in 38 recordings, while 16 videos showed no events. In 25 (66%) of the videos that showed events, additional measures such as haemostasis or suture repair were required. Common identified events were minor bleeding (n=39, 59%), thermal injury to non-target tissue (n=7, 11%), serosal tears (n=6, 9%). Common error mechanisms were ‘inadequate use of force/distance (too much)’ (n=20, 30%) and ‘inadequate visualisation’ during grasping/dissecting (n=6, 9%), ‘inadequate use of force/distance (too much)’ using an energy device (n=6, 9%), or during suturing (n=6, 9%). All events were recognised intraoperatively.ConclusionsAnalysis of successful operations allowed the identification of numerous error-event sequences. Reviewing injury mechanisms can enhance surgeons’ understanding of relevant errors. This error awareness may aid surgeons in preparing for cases, help avoid errors and mitigate their consequences. Thus, this approach may impact future surgical education and quality initiatives aimed at reducing surgical risks.
Immediate dispatch
Authors: Brown Richard 
Published: May 2015

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Immediate dispatch?’, was submitted and discussed by Richard Brown. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘The mating game’, which was published in the April issue of In Practice, appears on page 263.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Therapeutic use of methocarbamol in a demoiselle crane (Anthropoides virgo) with severe ataxia and lateroflexion of the neck
Authors: Done Lisa , Ialeggio Donna 
Published: May 2015

After running at high speed into a fence, an adult, male demoiselle crane (Anthropoides virgo), estimated age 20 years, presented with ataxia, inability to stand and severe lateroflexion of the base of the neck. Therapy for severe shock along with other supportive care treatments provided improvement. After the crane was transferred to a stall six days post presentation, it repeatedly ran into the walls, resulting in the inability to stand. Despite sling support and ongoing corticosteroid therapy, euthanasia was considered. The caudal cervical area was very stiff, with markedly reduced lateral and dorsoventral range of motion. Treatment with intravenous methocarbamol, a centrally acting muscle relaxant, was initiated. Within several hours of the first methocarbamol injection, the caudal cervical area became palpably more flexible. After 54 days of hospitalisation and 30 days of methocarbamol treatment, the crane was normal without clinical evidence of ataxia or lateroflexion of the neck.
Tracking and Functional Characterization of Epithelial–Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis
Authors: Ruscetti Marcus , Quach Bill , Dadashian Eman L. , Mulholland David J. , Wu Hong 
Published: May 2015

Abstract
The epithelial–mesenchymal transition (EMT) has been postulated as a mechanism by which cancer cells acquire the invasive and stem-like traits necessary for distant metastasis. However, direct in vivo evidence for the role of EMT in the formation of cancer stem–like cells (CSC) and the metastatic cascade remains lacking. Here we report the first isolation and characterization of mesenchymal-like and EMT tumor cells, which harbor both epithelial and mesenchymal characteristics, in an autochthonous murine model of prostate cancer. By crossing the established Pb-Cre+/−;PtenL/L;KrasG12D/+ prostate cancer model with a vimentin-GFP reporter strain, generating CPKV mice, we were able to isolate epithelial, EMT, and mesenchymal-like cancer cells based on expression of vimentin and EpCAM. CPKV mice (but not mice with Pten deletion alone) exhibited expansion of cells with EMT (EpCAM+/Vim-GFP+) and mesenchymal-like (EpCAM−/Vim-GFP+) characteristics at the primary tumor site and in circulation. These EMT and mesenchymal-like tumor cells displayed enhanced stemness and invasive character compared with epithelial tumor cells. Moreover, they displayed an enriched tumor-initiating capacity and could regenerate epithelial glandular structures in vivo, indicative of epithelia–mesenchyme plasticity. Interestingly, while mesenchymal-like tumor cells could persist in circulation and survive in the lung following intravenous injection, only epithelial and EMT tumor cells could form macrometastases. Our work extends the evidence that mesenchymal and epithelial states in cancer cells contribute differentially to their capacities for tumor initiation and metastatic seeding, respectively, and that EMT tumor cells exist with plasticity that can contribute to multiple stages of the metastatic cascade. Cancer Res; 75(13); 2749–59. ©2015 AACR.
A Novel Cinnamon-Related Natural Product with Pim-1 Inhibitory Activity Inhibits Leukemia and Skin Cancer
Authors: Kim Jong-Eun , Son Joe Eun , Jeong Hyein , Kim Dong Joon , Seo Sang Gwon , Lee Eunjung , Lim Tae Gyu , Kim Jong Rhan , Kimbung Yengo Raymond , Chen Hanyong , Bode Ann M. , Lee Ki Won , Dong Zigang 
Published: May 2015

Abstract
The Pim-1 kinase regulates cell survival, proliferation, and differentiation and is overexpressed frequently in many malignancies, including leukemia and skin cancer. In this study, we used kinase profiling analysis to demonstrate that 2′-hydroxycinnamicaldehyde (2′-HCA), a compound found in cinnamon, specifically inhibits Pim-1 activity. Cocrystallography studies determined the hydrogen bonding pattern between 2′-HCA and Pim-1. Notably, 2′-HCA binding altered the apo kinase structure in a manner that shielded the ligand from solvent, thereby acting as a gatekeeper loop. Biologically, 2′-HCA inhibited the growth of human erythroleukemia or squamous epidermoid carcinoma cells by inducing apoptosis. The compound was also effective as a chemopreventive agent against EGF-mediated neoplastic transformation. Finally, 2′-HCA potently suppressed the growth of mouse xenografts representing human leukemia or skin cancer. Overall, our results offered preclinical proof of concept for 2′-HCA as a potent anticancer principle arising from direct targeting of the Pim-1 kinase. Cancer Res; 75(13); 2716–28. ©2015 AACR.
A Monoclonal Antibody to ADAM17 Inhibits Tumor Growth by Inhibiting EGFR and Non–EGFR-Mediated Pathways
Authors: Rios-Doria Jonathan , Sabol Darrin , Chesebrough Jon , Stewart Dave , Xu Linda , Tammali Ravinder , Cheng Li , Du Qun , Schifferli Kevin , Rothstein Ray , Leow Ching Ching , Heidbrink-Thompson Jenny , Jin Xiaofang , Gao Changshou , Friedman Jay , Wilkinson Brandy , Damschroder Melissa , Pierce Andrew J. , Hollingsworth Robert E. , Tice David A. , Michelotti Emil F. 
Published: May 2015

Abstract
ADAM17 is the primary sheddase for HER pathway ligands. We report the discovery of a potent and specific ADAM17 inhibitory antibody, MEDI3622, which induces tumor regression or stasis in many EGFR-dependent tumor models. The inhibitory activity of MEDI3622 correlated with EGFR activity both in a series of tumor models across several indications as well in as a focused set of head and neck patient–derived xenograft models. The antitumor activity of MEDI3622 was superior to that of EGFR/HER pathway inhibitors in the OE21 esophageal model and the COLO205 colorectal model suggesting additional activity outside of the EGFR pathway. Combination of MEDI3622 and cetuximab in the OE21 model was additive and eradicated tumors. Proteomics analysis revealed novel ADAM17 substrates that function outside of the HER pathways and may contribute toward the antitumor activity of the monoclonal antibody. Mol Cancer Ther; 14(7); 1637–49. ©2015 AACR.
Predicting outcomes among patients with atrial fibrillation and heart failure receiving anticoagulation with warfarin
Authors: Ozonoff Al , Hylek Elaine M. , Berlowitz Dan R. , Ash Arlene S. , Miller Donald R. , Zhao Shibei , Reisman Joel I. , Jasuja Guneet K. , Rose Adam J. , Kim Eun-Jeong 
Published: May 2015

SummaryAmong patients receiving oral anticoagulation for atrial fibrillation (AF), heart failure (HF) is associated with poor anticoagulation control. However, it is not known which patients with heart failure are at greatest risk of adverse outcomes. We evaluated 62,156 Veterans Health Administration (VA) patients receiving warfarin for AF between 10/1/06–9/30/08 using merged VA-Medicare dataset. We predicted time in therapeutic range (TTR) and rates of adverse events by categorising patients into those with 0, 1, 2, or 3+ of five putative markers of HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline phosphatase> 150 U/l, serum sodium< 130 mEq/l, any receipt of metolazone, and any inpatient admission for HF exacerbation. These risk categories predicted TTR: patients without HF (referent) had a mean TTR of 65.0 %, while HF patients with 0, 1, 2, 3 or more markers had mean TTRs of 62.2 %, 57.2 %, 53.5 %, and 50.7 %, respectively (p< 0.001). These categories also discriminated for major haemorrhage well; compared to patients without HF, HF patients with increasing severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p< 0.001). However, although patients with HF had an elevated hazard for bleeding compared to those without HF, these categories did not effectively discriminate risk of ischaemic stroke across HF. In conclusion, we developed a HF severity model using easily available clinical characteristics that performed well to risk-stratify patients with HF who are receiving anticoagulation for AF with regard to major haemorrhage.
Role of moesin in HMGB1-stimulated severe inflammatory responses
Authors: Han Min-Su , Lee You-Mie , Kim Shin-Woo , Kim Kyung-Min , Lee Taeho , Lee Wonhwa , Kwon Oh Kwang , Lee Sangkyu , Bae Jong-Sup 
Published: May 2015

SummarySepsis is a life-threatening condition that arises when the body’s response to infection causes systemic inflammation. High-mobility group box 1 (HMGB1), as a late mediator of sepsis, enhances hyper-permeability, and it is therefore a therapeutic target. Despite extensive research into the underlying mechanisms of sepsis, the target molecules controlling vascular leakage remain largely unknown. Moesin is a cytoskeletal protein involved in cytoskeletal changes and para-cellular gap formation. The objectives of this study were to determine the roles of moesin in HMGB1-mediated vascular hyperpermeability and inflammatory responses and to investigate the mechanisms of action underlying these responses. Using siRNA knockdown of moesin expression in primary human umbilical vein endothelial cells (HUVECs), moesin was found to be required in HMGB1-induced F-actin rearrangement, hyperpermeability, and inflammatory responses. The mechanisms involved in moesin phosphorylation were analysed by blocking the binding of the HMGB1 receptor (RAGE) and inhibiting the Rho and MAPK pathways. HMGB1-treated HUVECs exhibited an increase in Thr558 phosphorylation of moesin. Circulating levels of moesin were measured in patients admitted to the intensive care unit with sepsis, severe sepsis, and septic shock; these patients showed significantly higher levels of moesin than healthy controls, which was strongly correlated with disease severity. High blood moesin levels were also observed in cecal ligation and puncture (CLP)-induced sepsis in mice. Administration of blocking moesin antibodies attenuated CLP-induced septic death. Collectively, our findings demonstrate that the HMGB1-RAGE-moesin axis can elicit severe inflammatory responses, suggesting it to be a potential target for the development of diagnostics and therapeutics for sepsis.