bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern of the Epitope-Specific IgG/IgM Response against Human Cytomegalovirus in Patients with Multiple Myeloma
Authors: Bogner Elke , Pecher Gabriele 
Published: June 2013

ABSTRACT
Human cytomegalovirus (HCMV) is a member of the herpesvirus family and represents a major human pathogen causing severe disease in newborns and immunocompromised patients, e.g., organ transplant recipients and patients with AIDS. One characteristic of herpesviruses is their ability to establish lifelong latency in their hosts; thus, reactivation during immunosuppression leads to recurrent episodes of disease. In several recent reports, it has been shown that HCMV infection may occur in patients with malignancy. This study focused on HCMV infection in patients with multiple myeloma (MM). In order to determine the IgM and IgG humoral immune response, sera from MM patients and healthy donors were analyzed with an accredited immunoblot test, and the IgM response was analyzed with an accredited enzyme-linked immunosorbent assay. A response against HCMV was detected in 80% of the MM patients. While the IgG pattern varied in each patient, the most prominent IgM response was against the tegument protein pp150 and two nonstructural proteins, the processivity factor (pUL44) and the single-stranded DNA binding protein (pUL57). An IgG avidity test revealed that 4 out of 20 MM patients had a fresh infection and 2 MM patients had a recent infection. The combination of IgG avidity and the IgM pattern will be a useful tool for reliable clinical diagnostics concerning HCMV and for application of early therapy for those MM patients suffering from a high viral load.
Challenges for Standardization of Clostridium difficile Typing Methods
Authors: Huber Charlotte A. , Foster Niki F. , Riley Thomas V. , Paterson David L. 
Published: June 2013

ABSTRACT

Typing of
Clostridium difficile
facilitates understanding of the epidemiology of the infection. Some evaluations have shown that certain strain types (for example, ribotype 027) are more virulent than others and are associated with worse clinical outcomes. Although restriction endonuclease analysis (REA) and pulsed-field gel electrophoresis have been widely used in the past, PCR ribotyping is the current method of choice for typing of
C. difficile
. However, global standardization of ribotyping results is urgently needed. Whole-genome sequencing of
C. difficile
has the potential to provide even greater epidemiologic information than ribotyping.
Multilocus Sequence Typing of Pneumocystis jirovecii from Clinical Samples: How Many and Which Loci Should Be Used?
Authors: Maitte Céline , Leterrier Marion , Le Pape Patrice , Miegeville Michel , Morio Florent 
Published: June 2013

ABSTRACT

Pneumocystis jirovecii
pneumonia (PCP) is an opportunistic infection with airborne transmission and remains a major cause of respiratory illness among immunocompromised individuals. In recent years, several outbreaks of PCP, occurring mostly in kidney transplant recipients, have been reported. Currently, multilocus sequence typing (MLST) performed on clinical samples is considered to be the gold standard for epidemiological investigations of nosocomial clusters of PCP. However, until now, no MLST consensus scheme has emerged. The aim of this study was to evaluate the discriminatory power of eight distinct loci previously used for the molecular typing of
P. jirovecii
(internal transcribed spacer 1 [ITS1], cytochrome
b
[
CYB
], mitochondrial rRNA gene [mt26S], large subunit of the rRNA gene [26S], superoxide dismutase [
SOD
], β-tubulin [β-
TUB
], dihydropteroate synthase [
DHPS
], and dihydrofolate reductase [
DHFR
]) using a cohort of 33 epidemiologically unrelated patients having respiratory samples that were positive for
P. jirovecii
and who were admitted to our hospital between 2006 and 2011. Our results highlight that the choice of loci for MLST is crucial, as the discriminatory power of the method was highly variable from locus to locus. In all, the eight-locus-based scheme we used displayed a high discriminatory power (Hunter [H] index, 0.996). Based on our findings, a simple and alternative MLST scheme relying on three loci only (mt26S,
CYB
, and
SOD
) provides enough discriminatory power (H-index, 0.987) to be used for preliminary investigations of nosocomial clusters of PCP.
Susceptibility Breakpoint for Enrofloxacin against Swine Salmonella spp
Authors: Hao Haihong , Pan Huafang , Ahmad Ijaz , Cheng Guyue , Wang Yulian , Dai Menghong , Tao Yanfei , Chen Dongmei , Peng Dapeng , Liu Zhenli , Huang Lingli , Yuan Zonghui 
Published: June 2013

ABSTRACTSusceptibility breakpoints are crucial for prudent use of antimicrobials. This study has developed the first susceptibility breakpoint (MIC ≤ 0.25 μg/ml) for enrofloxacin against swineSalmonellaspp. based on wild-type cutoff (COWT) and pharmacokinetic-pharmacodynamic (PK-PD) cutoff (COPD) values, consequently providing a criterion for susceptibility testing and clinical usage of enrofloxacin.
Fluoroquinolone-Resistant Haemophilus parasuis Isolates Exhibit More Putative Virulence Factors than Their Susceptible Counterparts
Authors: Zhang Qiang , Liu Jiantao , Yan Shuxian , Yang Yujie , Zhang Anding , Jin Meilin 
Published: June 2013

ABSTRACT

The prevalence of 23 putative virulence factors among fluoroquinolone-susceptible and -resistant
Haemophilus parasuis
isolates was analyzed. Putative hemolysin precursor, fimbrial assembly chaperone, and type I site-specific restriction modification system R subunit genes were more prevalent among fluoroquinolone-resistant
H. parasuis
isolates than among fluoroquinolone-susceptible
H. parasuis
isolates. Fluoroquinolone resistance may be associated with an increase in the presence of some virulence factors.
Retrovirus Restriction by TRIM5 Proteins Requires Recognition of Only a Small Fraction of Viral Capsid Subunits
Authors: Shi Jiong , Friedman David B. , Aiken Christopher 
Published: June 2013

ABSTRACT

The host restriction factors TRIM5α and TRIMCyp potently inhibit retrovirus infection by binding to the incoming retrovirus capsid. TRIM5 proteins are dimeric, and their association with the viral capsid appears to be enhanced by avidity effects owing to formation of higher-order oligomeric complexes. We examined the stoichiometric requirement for TRIM5 functional recognition by quantifying the efficiencies of restriction of HIV-1 and murine leukemia virus (MLV) particles containing various proportions of restriction-sensitive and -insensitive CA subunits. Both TRIMCyp and TRIM5α inhibited infection of retrovirus particles containing as little as 25% of the restriction-sensitive CA protein. Accordingly, we also observed efficient binding of TRIMCyp
in vitro
to capsid assemblies containing as little as one-fourth wild-type CA protein. Paradoxically, the ability of HIV-1 particles to abrogate TRIMCyp restriction in
trans
was more strongly dependent on the fraction of wild-type CA than was restriction of infection. Collectively, our results indicate that TRIM5 restriction factors bind to retroviral capsids in a highly cooperative manner and suggest that TRIM5 can engage a capsid lattice containing a minimum of three or fewer recognizable subunits per hexamer. Our study supports a model in which localized binding of TRIM5 to the viral capsid nucleates rapid polymerization of a TRIM5 lattice on the capsid surface.
Structure of the C-Terminal Domain of Lettuce Necrotic Yellows Virus Phosphoprotein
Authors: Martinez Nicolas , Ribeiro Euripedes A. , Leyrat Cédric , Tarbouriech Nicolas , Ruigrok Rob W. H. , Jamin Marc 
Published: June 2013

ABSTRACT

Lettuce necrotic yellows virus (LNYV) is a prototype of the plant-adapted cytorhabdoviruses. Through a meta-prediction of disorder, we localized a folded C-terminal domain in the amino acid sequence of its phosphoprotein. This domain consists of an autonomous folding unit that is monomeric in solution. Its structure, solved by X-ray crystallography, reveals a lollipop-shaped structure comprising five helices. The structure is different from that of the corresponding domains of other
Rhabdoviridae
,
Filoviridae
, and
Paramyxovirinae
; only the overall topology of the polypeptide chain seems to be conserved, suggesting that this domain evolved under weak selective pressure and varied in size by the acquisition or loss of functional modules.
Point Mutations in the Paramyxovirus F Protein That Enhance Fusion Activity Shift the Mechanism of Complement-Mediated Virus Neutralization
Authors: Johnson John B. , Schmitt Anthony P. , Parks Griffith D. 
Published: June 2013

ABSTRACTParainfluenza virus 5 (PIV5) activates and is neutralized by the alternative pathway (AP) in normal human serum (NHS) but not by heat-inactivated (HI) serum. We have tested the relationship between the fusion activity within the PIV5 F protein, the activation of complement pathways, and subsequent complement-mediated virus neutralization. Recombinant PIV5 viruses with enhanced fusion activity were generated by introducing point mutations in the F fusogenic peptide (G3A) or at a distal site near the F transmembrane domain (S443P). In contrast to wild-type (WT) PIV5, the mutant G3A and S443P viruses were neutralized by both NHS and HI serum. Unlike WT PIV5, hyperfusogenic G3A and S443P viruses were potent C4 activators, C4 was deposited on NHS-treated mutant virions, and the mutants were neutralized by factor B-depleted serum but not by C4-depleted serum. Antibodies purified from HI human serum were sufficient to neutralize both G3A and S443P virusesin vitrobut were ineffective against WT PIV5. Electron microscopy data showed greater deposition of purified human antibodies on G3A and S443P virions than on WT PIV5 particles. These data indicate that single amino acid changes that enhance the fusion activity of the PIV5 F protein shift the mechanism of complement activation in the context of viral particles or on the surface of virus-infected cells, due to enhanced binding of antibodies. We present general models for the relationship between enhanced fusion activity in the paramyxovirus F protein and increased susceptibility to antibody-mediated neutralization.
Imaging of the Alphavirus Capsid Protein during Virus Replication
Authors: Zheng Yan , Kielian Margaret 
Published: June 2013

ABSTRACT
Alphaviruses are enveloped viruses with highly organized structures. The nucleocapsid (NC) core contains a capsid protein lattice enclosing the plus-sense RNA genome, and it is surrounded by a lipid bilayer containing a lattice of the E1 and E2 envelope glycoproteins. Capsid protein is synthesized in the cytoplasm and particle budding occurs at the plasma membrane (PM), but the traffic and assembly of viral components and the exit of virions from host cells are not well understood. To visualize the dynamics of capsid protein during infection, we developed a Sindbis virus infectious clone tagged with a tetracysteine motif. Tagged capsid protein could be fluorescently labeled with biarsenical dyes in living cells without effects on virus growth, morphology, or protein distribution. Live cell imaging and colocalization experiments defined distinct groups of capsid foci in infected cells. We observed highly motile internal puncta that colocalized with E2 protein, which may represent the transport machinery that capsid protein uses to reach the PM. Capsid was also found in larger nonmotile internal structures that colocalized with cellular G3BP and viral nsP3. Thus, capsid may play an unforeseen role in these previously observed G3BP-positive foci, such as regulation of cellular stress granules. Capsid puncta were also observed at the PM. These puncta colocalized with E2 and recruited newly synthesized capsid protein; thus, they may be sites of virus assembly and egress. Together, our studies provide the first dynamic views of the alphavirus capsid protein in living cells and a system to define detailed mechanisms during alphavirus infection.
A 20-Year Prospective Study of Plasma Prolactin as a Risk Marker of Breast Cancer Development
Authors: Tworoger Shelley S. , Eliassen A. Heather , Zhang Xuehong , Qian Jing , Sluss Patrick M. , Rosner Bernard A. , Hankinson Susan E. 
Published: June 2013

Abstract
Understanding how the timing of exposure to endogenous hormones influences cancer development is critical to elucidating disease etiology. Prolactin increases proliferation and cell motility, processes important in later stage tumor development, suggesting that levels proximate (versus distant) to diagnosis may better predict risk. Thus, we calculated relative risks (RR) and 95% confidence intervals (CI) for prolactin levels on samples collected &lt;10 (proximate) versus ≥10 (distant) years before diagnosis in the Nurses' Health Study (NHS) and NHSII with breast cancer risk, including in a subset of NHS women providing two samples 10 years apart. We measured prolactin via immunoassay in cases diagnosed from 1990 to 2010 (NHS) and 1999 to 2009 (NHSII) and matched controls. Overall, 2,468 cases and 4,021 controls had prolactin measured &lt;10 years and 953 cases and 1,339 controls &gt;10 years before diagnosis/reference date. There was an increased risk for higher proximate prolactin levels [RR, &gt;15.7 vs. ≤8.1 ng/mL (i.e., top vs. bottom quartiles) = 1.20; 95% CI, 1.03–1.40; Ptrend = 0.005], but not for distant levels (RR = 0.97; Ptrend = 0.94); results were similar among women with two blood samples (Pinteraction, proximate vs. distant = 0.07). The positive association was stronger for ER+ disease (RR = 1.28; Ptrend = 0.003) and postmenopausal women (RR = 1.37; Ptrend = 0.0002). Among postmenopausal women, the association was strongest for ER+ disease (RR = 1.52) and lymph node-positive cases (RR = 1.63). Our data suggest that prolactin levels measured &lt;10 years before diagnosis are most strongly associated with postmenopausal breast cancer risk, especially for ER+ tumors and metastatic disease. This corresponds with biologic data that prolactin is etiologically important in tumor promotion. Cancer Res; 73(15); 4810–9. ©2013 AACR.
TH2 Cytokines from Malignant Cells Suppress TH1 Responses and Enforce a Global TH2 Bias in Leukemic Cutaneous T-cell Lymphoma
Authors: Guenova Emmanuella , Watanabe Rei , Teague Jessica E. , Desimone Jennifer A. , Jiang Ying , Dowlatshahi Mitra , Schlapbach Christoph , Schaekel Knut , Rook Alain H. , Tawa Marianne , Fisher David C. , Kupper Thomas S. , Clark Rachael A. 
Published: June 2013

Abstract
Purpose: In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (TH)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, TH2 and TH17 cells.
Experimental Design: We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL.
Results: Twelve out of 12 patients with L-CTCL overproduced TH2 cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFNγ production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden.
Conclusions: A global TH2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 cytokines from malignant cells strongly inhibited TH1 responses. Our results suggest that therapies that inhibit TH2 cytokine activity, by virtue of their ability to improve TH1 responses, may have the potential to enhance both anticancer and antipathogen responses. Clin Cancer Res; 19(14); 3755–63. ©2013 AACR.
“License to Kill” Reflects Joint Action of CD4 and CD8 T Cells
Authors: Melief Cornelis J.M. 
Published: June 2013

Abstract
The spontaneous T-cell responses to the KIF20A cancer-associated antigen found by Tomita and colleagues among peripheral blood mononuclear cells of patients with cancer, but not healthy people, involve both CD4 and CD8 T cells. Synthetic long peptides of KIF20A stimulate synergy between these two T-cell types to promote cancer cell killing. Clin Cancer Res; 19(16); 4295–6. ©2013 AACR.
12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity
Authors: Yeung Jennifer , Apopa Patrick L. , Vesci Joanne , Stolla Moritz , Rai Ganesha , Simeonov Anton , Jadhav Ajit , Fernandez-Perez Pilar , Maloney David J. , Boutaud Olivier , Holman Theodore R. , Holinstat Michael 
Published: June 2013

SummaryFollowing initial platelet activation, arachidonic acid is metabolised by cyclooxygenase-1 and 12-lipoxygenase (12-LOX). While the role of 12-LOX in the platelet is not well defined, recent evidence suggests that it may be important for regulation of platelet activity and is agonist- specific in the manner in which it regulates platelet function. Using small molecule inhibitors selective for 12-LOX and 12-LOX-deficient mice, the role of 12-LOX in regulation of human platelet activation and thrombosis was investigated. Pharmacologically inhibiting 12-LOX resulted in attenuation of platelet aggregation, selective inhibition of dense versus alpha granule secretion, and inhibition of platelet adhesion under flow for PAR4 and collagen. Additionally, 12-LOX-deficient mice showed attenuated integrin activity to PAR4-AP and convulxin compared to wild-type mice. Finally, platelet activation by PARs was shown to be differentially dependent on COX-1 and 12-LOX with PAR1 relying on COX-1 oxidation of arachidonic acid while PAR4 being more dependent on 12-LOX for normal platelet function. These studies demonstrate an important role for 12-LOX in regulating platelet activation and thrombosis. Furthermore, the data presented here provide a basis for potentially targeting 12-LOX as a means to attenuate unwanted platelet activation and clot formation.
G
βγ
-Independent Recruitment of G-Protein Coupled Receptor Kinase 2 Drives Tumor Necrosis Factor α–Induced Cardiac β-Adrenergic Receptor Dysfunction
Authors: Vasudevan Neelakantan T. , Mohan Maradumane L. , Gupta Manveen K. , Martelli Elizabeth E. , Hussain Afshan K. , Qin Yilu , Chandrasekharan Unni M. , Young David , Feldman Arthur M. , Sen Subha , Dorn Gerald W. , DiCorleto Paul E. , Prasad Sathyamangla V. Naga 
Published: June 2013

Background—
Proinflammatory cytokine tumor necrosis factor-α (TNFα) induces β-adrenergic receptor (βAR) desensitization, but mechanisms proximal to the receptor in contributing to cardiac dysfunction are not known.

Methods and Results—

Two different proinflammatory transgenic mouse models with cardiac overexpression of myotrophin (a prohypertrophic molecule) or TNFα showed that TNFα alone is sufficient to mediate βAR desensitization as measured by cardiac adenylyl cyclase activity. M-mode echocardiography in these mouse models showed cardiac dysfunction paralleling βAR desensitization independent of sympathetic overdrive. TNFα-mediated βAR desensitization that precedes cardiac dysfunction is associated with selective upregulation of G-protein coupled receptor kinase 2 (GRK2) in both mouse models. In vitro studies in β
2
AR-overexpressing human embryonic kidney 293 cells showed significant βAR desensitization, GRK2 upregulation, and recruitment to the βAR complex following TNFα. Interestingly, inhibition of phosphoinositide 3-kinase abolished GRK2-mediated βAR phosphorylation and GRK2 recruitment on TNFα. Furthermore, TNFα-mediated βAR phosphorylation was not blocked with βAR antagonist propranolol. Additionally, TNFα administration in transgenic mice with cardiac overexpression of G
βγ
-sequestering peptide βARK-ct could not prevent βAR desensitization or cardiac dysfunction showing that GRK2 recruitment to the βAR is G
βγ
independent. Small interfering RNA knockdown of GRK2 resulted in the loss of TNFα-mediated βAR phosphorylation. Consistently, cardiomyocytes from mice with cardiac-specific GRK2 ablation normalized the TNFα-mediated loss in contractility, showing that TNFα-induced βAR desensitization is GRK2 dependent.

Conclusions—

TNFα-induced βAR desensitization is mediated by GRK2 and is independent of G
βγ
, uncovering a hitherto unknown cross-talk between TNFα and βAR function, providing the underpinnings of inflammation-mediated cardiac dysfunction.
Transitions: Refugees and Natives
Authors: Tuitt Patricia 
Published: June 2013

European Directive 2004/83 (the ‘Qualification Directive’) limits claims for asylum to those refugees coming from outside of the European Union. This provision institutionalises a long established practice in which member states of the European Union are presumed to be safe countries of origin and safe countries of asylum. This article argues that the European Union could not have come into being without producing refugees. With reference to the definition of refugee enshrined within Article 1.A (2) of the Convention Relating to the Status of Refugees1 and the jurisprudence surrounding one key qualifying element of the definition – persecution – the article seeks to explore how the international law governing the status of refugee has been deployed to deny that the European Union is a place of origin of refugees.
The Making of a Reflective Practitioner of Mission: What Shaped the Author of Christianity Rediscovered
Authors: Bowen John P. 
Published: June 2013

Abstract
Vincent Donovan is best known for his best-selling Christianity Rediscovered (1978, 2003), frequently cited in discussions of the mission of the church in the post-Christendom West. His recently published letters from Tanzania between 1957 and 1973 shed new light on the man and his development. This article identifies some of the influences that shaped Donovan: firstly, the significance of the changing political face of Africa at that time, and how it led Donovan to question what this meant for the future of missions in Africa. Secondly, there were ecclesial influences. One was the character of his Order (the Spiritans) which found a fresh opportunity to experiment with enculturation when a new diocese was founded in Arusha in 1963, led by a Spiritan bishop. The other ecclesial influence was that of Vatican II, to which Spiritans contributed and which (they felt) affirmed their direction – though they also felt it did not go far enough. Thirdly, the letters show Donovan’s personal development from his arrival in Africa in 1957 as a naïve young missionary to the seasoned missiologist concerned “to fill the flesh and blood of Africa with the soul of Christianity” whose story is told in Christianity Rediscovered.