bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Host Gene Expression Changes Reveals Distinct Roles for the Cytoplasmic Domain of the Epstein-Barr Virus Receptor/CD21 in B-Cell Maturation, Activation, and Initiation of Virus Infection
Authors: Arredouani Mohamed S. , Bhasin Manoj K. , Sage David R. , Dunn Laura K. , Gill Michael B. , Agnani Deep , Libermann Towia A. , Fingeroth Joyce D. 
Published: March 2014

ABSTRACTEpstein-Barr virus (EBV) attachment to human CD21 on the B-cell surface initiates infection. Whether CD21 is a simple tether or conveys vital information to the cell interior for production of host factors that promote infection of primary B cells is controversial, as the cytoplasmic fragment of CD21 is short, though highly conserved. The ubiquity of CD21 on normal B cells, the diversity of this population, and the well-known resistance of primary B cells to gene transfer technologies have all impeded resolution of this question. To uncover the role(s) of the CD21 cytoplasmic domain during infection initiation, the full-length receptor (CD21 = CR), a mutant lacking the entire cytoplasmic tail (CT), and a control vector (NEO) were stably expressed in two pre-B-cell lines that lack endogenous receptor. Genome-wide transcriptional analysis demonstrated that stable CD21 surface expression alone (either CR or CT) produced multiple independent changes in gene expression, though both dramatically decreased class I melanoma-associated antigen (MAGE) family RNAs and upregulated genes associated with B-cell differentiation (e.g., C2TA, HLA-II, IL21R, MIC2, CD48, and PTPRCAP/CD45-associated protein). Temporal analysis spanning 72 h revealed that not only CR- but also CT-expressing lines initiated latency. In spite of this, the number and spectrum of transcripts altered in CR- compared with CT-bearing lines at 1 h after infection further diverged. Differential modulation of immediate early cellular transcripts (e.g., c-Jun and multiple histones), both novel and previously linked to CD21-initiated signaling, as well as distinct results from pathway analyses support a separate role for the cytoplasmic domain in initiation of intracellular signals.IMPORTANCEMembrane proteins that mediate virus attachment tether virus particles to the cell surface, initiating infection. In addition, upon virus interaction such proteins may transmit signals to the interior of the cell that support subsequent steps in the infection process. Here we show that expression of the Epstein-Barr virus B-cell attachment receptor, CD21, in B cells that lack this receptor results in significant changes in gene expression, both before and rapidly following EBV-CD21 interaction. These changes translate into major signaling pathway alterations that are predicted to support stable infection.
The Crystal Structure of a Cardiovirus RNA-Dependent RNA Polymerase Reveals an Unusual Conformation of the Polymerase Active Site
Authors: Vives-Adrian Laia , Lujan Celia , Oliva Baldo , van der Linden Lonneke , Selisko Barbara , Coutard Bruno , Canard Bruno , van Kuppeveld Frank J. M. , Ferrer-Orta Cristina , Verdaguer Núria 
Published: March 2014

ABSTRACT

Encephalomyocarditis virus (EMCV) is a member of the
Cardiovirus
genus within the large
Picornaviridae
family, which includes a number of important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3D
pol
is a key enzyme for viral genome replication. In this study, we report the X-ray structures of two different crystal forms of the EMCV RdRp determined at 2.8- and 2.15-Å resolution. The
in vitro
elongation and VPg uridylylation activities of the purified enzyme have also been demonstrated. Although the overall structure of EMCV 3D
pol
is shown to be similar to that of the known RdRps of other members of the
Picornaviridae
family, structural comparisons show a large reorganization of the active-site cavity in one of the crystal forms. The rearrangement affects mainly motif A, where the conserved residue Asp240, involved in ribonucleoside triphosphate (rNTP) selection, and its neighbor residue, Phe239, move about 10 Å from their expected positions within the ribose binding pocket toward the entrance of the rNTP tunnel. This altered conformation of motif A is stabilized by a cation-π interaction established between the aromatic ring of Phe239 and the side chain of Lys56 within the finger domain. Other contacts, involving Phe239 and different residues of motif F, are also observed. The movement of motif A is connected with important conformational changes in the finger region flanked by residues 54 to 63, harboring Lys56, and in the polymerase N terminus. The structures determined in this work provide essential information for studies on the cardiovirus RNA replication process and may have important implications for the development of new antivirals targeting the altered conformation of motif A.

IMPORTANCE
The
Picornaviridae
family is one of the largest virus families known, including many important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3D
pol
is a key enzyme for picornavirus genome replication and a validated target for the development of antiviral therapies. Solving the X-ray structure of the first cardiovirus RdRp, EMCV 3D
pol
, we captured an altered conformation of a conserved motif in the polymerase active site (motif A) containing the aspartic acid residue involved in rNTP selection and binding. This altered conformation of motif A, which interferes with the correct positioning of the rNTP substrate in the active site, is stabilized by a number of residues strictly conserved among picornaviruses. The rearrangements observed suggest that this motif A segment is a dynamic element that can be modulated by external effectors, either activating or inhibiting enzyme activity, and this type of modulation appears to be general to all picornaviruses.
Combined Adenovirus Vector and Hepatitis C Virus Envelope Protein Prime-Boost Regimen Elicits T Cell and Neutralizing Antibody Immune Responses
Authors: Chmielewska Alicja M. , Naddeo Mariarosaria , Capone Stefania , Ammendola Virginia , Hu Ke , Meredith Luke , Verhoye Lieven , Rychlowska Malgorzata , Rappuoli Rino , Ulmer Jeffrey B. , Colloca Stefano , Nicosia Alfredo , Cortese Riccardo , Leroux-Roels Geert , Balfe Peter , Bienkowska-Szewczyk Krystyna , Meuleman Philip , McKeating Jane A. , Folgori Antonella 
Published: March 2014

ABSTRACT

Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8
+
and CD4
+
T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to-cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone.

IMPORTANCE
HCV infection is a major health problem. Despite the availability of new directly acting antiviral agents for treating chronic infection, an affordable preventive vaccine provides the best long-term goal for controlling the global epidemic. This report describes a new anti-HCV vaccine targeting the envelope viral proteins based on adenovirus vector and protein in adjuvant. Rodents primed with the adenovirus vaccine and boosted with the adjuvanted protein developed cross-neutralizing antibodies and potent T cell responses that surpassed immune responses achieved with either vaccine component alone. If combined with the adenovirus vaccine targeting the HCV NS antigens now under clinical testing, this new vaccine might lead to a stronger and broader immune response and to a more effective vaccine to prevent HCV infection. Importantly, the described approach represents a valuable strategy for other infectious diseases in which both T and B cell responses are essential for protection.
Improving the preoperative care of patients with femoral neck fractures through the development and implementation of a checklist
Authors: Agha Riaz , Edison Eric , Fowler Alexander 
Published: March 2014

AbstractThe incidence of femoral neck fractures (FNFs) is expected to rise with life expectancy. It is important to improve the safety of these patients whilst under the care of orthopaedic teams.This study aimed to increase the performance of vital preoperative tasks in patients admitted for femoral neck fracture operations by producing and implementing a checklist as an aide memoir. The checklist was designed primarily for use by senior house officers (SHOs) admitting patients from the emergency department.A list of 12 preoperative tasks was identified. A baseline audit of 10 random patients showed that the mean proportion of the 12 tasks completed was 53% (range 25% - 83%). A survey of 14 nurses and surgeons found that the majority of respondents agreed that there was a problem with the performance of most of the tasks. The tasks were incorporated into a checklist which was refined in three plan-do-study-act cycles and introduced into the femoral neck fracture pathway.In the week following the introduction of the checklist, 77% of the checklist tasks were completed, 24% more than at the baseline audit (53%). In week 3, the completion of checklist tasks rose to 88% and to 95% in week 4.In conclusion, a simple checklist can markedly improve the performance and recording of preoperative tasks by SHOs. We recommend the wider adoption of the new checklist to be produced as a sticker for patients’ medical records. Further study is required to ascertain the effect of the checklist on clinical outcomes.
Looking a store horse in the mouth
Authors: Collins Joe 
Published: March 2014

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, ‘Looking a store horse in the mouth’, was submitted and is discussed by Joe Collins. 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 case of the whelping bitch’, which was published in the February issue of In Practice, appears on page 159.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.
Studies of construction methods for Bentonite engineered barrier systems for sub-surface disposal: vibratory compaction
Authors: Yamada Atsuo , Akiyama Yoshihiro , Nakajima Masaki , Yada Tsutomu , Chijimatsu Masakazu , Nakajima Takahiro 
Published: March 2014

Abstract

Bentonite buffer is a part of the engineered barrier systems (EBS) for sub-surface disposal. The EBS is required to meet two quality standards at completion of construction. One is very low permeability of less than 5×10
−13
m s
−1
and the other is very low diffusibility of less than 1×10
−12
m
2
s
−1
. The bentonite buffer is required for the first quality standard of low permeability and must be constructed with high density in order to make the buffer a low-permeability layer. To confirm that the bentonite buffer is actually constructed with high density, we have carried out a full-scale mock-up test for part of the Demonstration Test of Underground Cavern-Type Disposal Facilities commissioned by the Japanese government in fiscal year 2005. This paper covers the test results from the construction of the bentonite buffer.
Optimization of Natural Killer T Cell–Mediated Immunotherapy in Cancer Using Cell-Based and Nanovector Vaccines
Authors: Faveeuw C. , Trottein F. 
Published: March 2014

Abstractα-Galactosylceramide (α-GalCer) represents a new class of immune stimulators and vaccine adjuvants that activate type I natural killer T (NKT) cells to swiftly release cytokines and to exert helper functions for acquired immune responses. This unique property prompted clinicians to exploit the antitumor potential of NKT cells. Here, we review the effects of α-GalCer in (pre)clinics and discuss current and future strategies that aim to optimize NKT cell–mediated antitumor therapy, with a particular focus on cell-based and nanovector vaccines. Cancer Res; 74(6); 1632–8. ©2014 AACR.
Noncanonical Functions of Telomerase: Implications in Telomerase-Targeted Cancer Therapies
Authors: Li Yinghui , Tergaonkar Vinay 
Published: March 2014

Abstract
Telomerase plays a pivotal role in bypassing cellular senescence and maintaining telomere homeostasis, essential properties required for the sustenance and progression of cancer. However, recent investigations have uncovered extratelomeric properties of telomerase that are independent of its role in telomere extension. This review summarizes recent insights to the noncanonical functions of telomerase reverse transcriptase (TERT) catalytic subunit, in particular in cancer progression, and highlights two major signaling mechanisms involved in the cross-talk with TERT—the NF-κB and Wnt/β-catenin pathways. We propose a feed-forward regulatory loop mechanism underlying TERT activation in cancers in which TERT acts as a transcriptional modulator of oncogenic signaling pathways that sustain its own levels and control the induction of target genes critical for tumor cell survival and proliferation. Finally, we provide a new perspective on telomerase-targeted cancer therapies and suggest possible interventions targeting the nontelomeric roles of TERT. This therapeutic strategy can be used in the future targeting of other telomerase components that exhibit novel nontelomeric functions in cancer and other ailments. Cancer Res; 74(6); 1639–44. ©2014 AACR.
Beyond Histology: Translating Tumor Genotypes into Clinically Effective Targeted Therapies
Authors: Meador Catherine B. , Micheel Christine M. , Levy Mia A. , Lovly Christine M. , Horn Leora , Warner Jeremy L. , Johnson Douglas B. , Zhao Zhongming , Anderson Ingrid A. , Sosman Jeffrey A. , Vnencak-Jones Cindy L. , Dahlman Kimberly B. , Pao William 
Published: March 2014

Abstract
Increased understanding of intertumoral heterogeneity at the genomic level has led to significant advancements in the treatment of solid tumors. Functional genomic alterations conferring sensitivity to targeted therapies can take many forms, and appropriate methods and tools are needed to detect these alterations. This review provides an update on genetic variability among solid tumors of similar histologic classification, using non–small cell lung cancer and melanoma as examples. We also discuss relevant technological platforms for discovery and diagnosis of clinically actionable variants and highlight the implications of specific genomic alterations for response to targeted therapy. Clin Cancer Res; 20(9); 2264–75. ©2014 AACR.
SERMs Attenuate Estrogen-Induced Malignant Transformation of Human Mammary Epithelial Cells by Upregulating Detoxification of Oxidative Metabolites
Authors: Hemachandra L.P. Madhubhani P. , Patel Hitisha , Chandrasena R. Esala P. , Choi Jaewoo , Piyankarage Sujeewa C. , Wang Shuai , Wang Yijin , Thayer Emily N. , Scism Robert A. , Michalsen Bradley T. , Xiong Rui , Siklos Marton I. , Bolton Judy L. , Thatcher Gregory R.J. 
Published: March 2014

Abstract
The risk of developing hormone-dependent cancers with long-term exposure to estrogens is attributed both to proliferative, hormonal actions at the estrogen receptor (ER) and to chemical carcinogenesis elicited by genotoxic, oxidative estrogen metabolites. Nontumorigenic MCF-10A human breast epithelial cells are classified as ER− and undergo estrogen-induced malignant transformation. Selective estrogen receptor modulators (SERM), in use for breast cancer chemoprevention and for postmenopausal osteoporosis, were observed to inhibit malignant transformation, as measured by anchorage-independent colony growth. This chemopreventive activity was observed to correlate with reduced levels of oxidative estrogen metabolites, cellular reactive oxygen species (ROS), and DNA oxidation. The ability of raloxifene, desmethylarzoxifene (DMA), and bazedoxifene to inhibit this chemical carcinogenesis pathway was not shared by 4-hydroxytamoxifen. Regulation of phase II rather than phase I metabolic enzymes was implicated mechanistically: raloxifene and DMA were observed to upregulate sulfotransferase (SULT 1E1) and glucuronidase (UGT 1A1). The results support upregulation of phase II metabolism in detoxification of catechol estrogen metabolites leading to attenuated ROS formation as a mechanism for inhibition of malignant transformation by a subset of clinically important SERMs. Cancer Prev Res; 7(5); 505–15. ©2014 AACR.
Deep-water species of Crangonidae and Glyphocrangonidae (Decapoda, Caridea) collected during the TALUD XV cruise off the west coast of southern Baja California, Mexico
Authors: Hendrickx Michel E. 
Published: March 2014

Four species of Crangonidae and Glyphocrangonidae were collected during a survey of the deep-water fauna off the west coast of the southern part of the Baja California Peninsula, Mexico. A total of 168 specimens were collected, with a clear dominance of Glyphocrangon spinulosa Faxon, 1893 (85% of collected specimens). A new northernmost distribution limit is set for Paracrangon areolata Faxon, 1893, Sclerocrangon atrox Faxon, 1893 and Glyphocrangon alata Faxon, 1893, while first records are made available for G. spinulosa off the west coast of the Baja California Peninsula.
Diversity and bathymetric distribution of decapod crustaceans attracted to baited traps from the middle slope of the northern Aegean Sea
Authors: Gönülal O. , Sezgin M. , Öztürk B. 
Published: March 2014

We sampled the decapod crustaceans inhabiting the depth zone between 500 and 1500 m off Gökçeada Island (northern Aegean Sea) from May 2010 to November 2011. The deep-slope decapod fauna of the northern Aegean Sea was sampled with baited traps. A total of 23 species of decapods have been identified at 32 stations. The results were analysed in terms of composition and distribution of benthic and benthopelagic bait-attracted species between regions. In addition, they were compared between stations in relation to the depth gradient. The results are discussed in relation to previous studies carried out in the eastern and western Mediterranean. Also, the use of traps is commented for different regions and the effects of the sampler on benthic species are discussed. The most common species was the penaeid shrimp, Parapenaeus longirostris in samples taken between 500 and 600 m. It is followed by Polycheles typhlops and the pandalid shrimp Plesionika martia martia. These species constitute more than 50% of all decapods. Differences among the strata at 500-1500 m depth were tentatively explained using the Shannon-Weaver diversity index (H′). The highest H′ value was found for the 800-1000 m depth strata. The lowest number of species was observed between 1000 and 1500 m, which lowered the diversity index values (H′). The results of similarity percentage analysis (SIMPER) showed a change in the decapod fauna below 1000 m depth. The present results are preliminary; further data collection and analysis will be required to evaluate the role of palaeoecolgical conditions and trophic factors, and how these could be supposed to interact.
Defining subgroups of low socioeconomic status women at risk for depressive symptoms: The importance of perceived stress and cumulative risks
Authors: van der Waerden Judith EB , Hoefnagels Cees , Hosman Clemens MH , Jansen Maria WJ 
Published: March 2014

Background: Most disadvantaged women are exposed to risk factors for depression, but not all necessarily have an identical risk for this mental health problem. A better prediction of which low socioeconomic status (SES) women are most at risk for depressive symptoms can help target preventive interventions at high-risk subgroups most in need of support. Aims: Exploring which demographic, socioeconomic and psychological risk factors are associated with self-reported depressive symptoms in a sample of low-SES women and whether the number of risk factors might expose them to an accumulated risk. Methods: Between April 2005 and November 2007, 519 disadvantaged women from urban neighbourhoods in Maastricht, a southern Dutch city, participated in a cross-sectional survey on stress and depressive symptoms. Results: Lower education levels, no current employment and lower net monthly family incomes were socioeconomic risk factors associated with higher scores for depressive symptoms. The psychological risk factor ‘perceived stress’ had the highest explained variance and was most strongly associated with depressive symptoms. Women exposed to multiple risk factors across domains had a cumulated risk for depressive symptomatology. Conclusion: Low-SES women who seem most eligible for targeted preventive action are those with cumulative risks. Depression prevention strategies for this population may benefit from focusing on perceived stress since this is an important modifiable risk factor.
Outcomes of Holmium Laser–Assisted Lithotripsy with Sialendoscopy in Treatment of Sialolithiasis
Authors: Phillips James , Withrow Kirk 
Published: March 2014

ObjectivesThe purpose of the current study was to compare outcomes and complication rates of sialolithiasis treated with intracorporeal holmium laser lithotripsy in conjunction with salivary endoscopy with those treated with simple basket retrieval or a combined endoscopic/open procedure.Study DesignCase‐comparison study.SettingTertiary hospital.MethodsReview of prospectively collected data of patients who underwent treatment for sialolithiasis by the senior author during 2011 to 2013. Patient demographics, operative techniques, surgical findings, clinical outcomes, and complications were recorded. Additional information regarding symptoms and satisfaction with treatment was obtained via standardized telephone questionnaire at the time of the data analysis.ResultsThirty‐one patients were treated for sialolithiasis. Sialoliths averaged 5.9 mm in size (range, 2‐20 mm) and were comparable between both groups. Sixty‐eight percent were in the submandibular gland (n = 21), with the remaining 32% in the parotid gland (n = 10). Fifty‐two percent of patients (n = 16) were treated endoscopically with intracorporeal holmium laser lithotripsy, while the remaining 48% (n = 15) were treated with salivary endoscopy techniques other than laser lithotripsy. Successful stone removal without additional maneuvers occurred in 81% of the laser cases and 93% of the nonlaser group. Patients in the laser group reported an average improvement of symptoms of 95% compared with 90% of the nonlaser group when adjusted for outliers. Complications in all patients included ductal stenosis (n = 2) and salivary fistula (n = 1).ConclusionThe results of our series show favorable results with the use of intracorporeal holmium laser lithotripsy for the endoscopic management of sialolithiasis with minimal adverse events.