bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between malaria exposure and Kaposi's sarcoma‐associated herpes virus seropositivity in Uganda
Authors: Nalwoga Angela , Cose Stephen , Wakeham Katie , Miley Wendell , Ndibazza Juliet , Drakeley Christopher , Elliott Alison , Whitby Denise , Newton Robert 
Published: January 2015

AbstractObjectiveUnlike other herpes viruses, Kaposi's sarcoma‐associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub‐Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV.MethodsAntibodies against P. falciparum merozoite surface protein (PfMSP)‐1, P. falciparum apical membrane antigen (PfAMA)‐1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children.ResultsKaposi's sarcoma‐associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP‐1 and PfAMA‐1, respectively (P < 0.0001). Among children, only antibodies to PfAMA‐1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti‐ORF73 antibodies were more strongly associated with malaria antibodies than anti‐K8.1 antibodies.ConclusionThe association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.
LATERAL ORGAN BOUNDARIES DOMAIN (LBD)10 interacts with SIDECAR POLLEN/LBD27 to control pollen development in Arabidopsis
Authors: Kim Min‐Jung , Kim Mirim , Lee Mi Rha , Park Soon Ki , Kim Jungmook 
Published: January 2015

SummaryDuring male gametophyte development in Arabidopsis thaliana, the microspores undergo an asymmetric division to produce a vegetative cell and a generative cell, which undergoes a second division to give rise to two sperm cells. SIDECAR POLLEN/LATERAL ORGAN BOUNDARIES DOMAIN (LBD) 27 plays a key role in the asymmetric division of microspores. Here we provide molecular genetic evidence that a combinatorial role of LBD10 with LBD27 is crucial for male gametophyte development in Arabidopsis. Expression analysis, genetic transmission and pollen viability assays, and pollen development analysis demonstrated that LBD10 plays a role in the male gametophyte function primarily at germ cell mitosis. In the mature pollen of lbd10 and lbd10 expressing a dominant negative version of LBD10, LBD10:SRDX, aberrant microspores such as bicellular and smaller tricellular pollen appeared at a ratio of 10–15% with a correspondingly decreased ratio of normal tricellular pollen, whereas in lbd27 mutants, 70% of the pollen was aborted. All pollen in the lbd10 lbd27 double mutants was aborted and severely shrivelled compared with that of the single mutants, indicating that LBD10 and LBD27 are essential for pollen development. Gene expression and subcellular localization analyses of LBD10:GFP and LBD27:RFP during pollen development indicated that posttranscriptional and/or posttranslational controls are involved in differential accumulation and subcellular localization of LBD10 and LBD27 during pollen development, which may contribute in part to combinatorial and distinct roles of LBD10 with LBD27 in microspore development. In addition, we showed that LBD10 and LBD27 interact to form a heterodimer for nuclear localization.
Data consistency conditions for truncated fanbeam and parallel projections
Authors: Clackdoyle Rolf , Desbat Laurent 
Published: January 2015

Purpose:In image reconstruction from projections, data consistency conditions (DCCs) are mathematical relationships that express the overlap of information between ideal projections. DCCs have been incorporated in image reconstruction procedures for positron emission tomography, single photon emission computed tomography, and x‐ray computed tomography (CT). Building on published fanbeam DCCs for nontruncated projections along a line, the authors recently announced new DCCs that can be applied to truncated parallel projections in classical (two‐dimensional) image reconstruction. These DCCs take the form of polynomial expressions for a weighted backprojection of the projections. The purpose of this work was to present the new DCCs for truncated parallel projections, to extend these conditions to truncated fanbeam projections on a circular trajectory, to verify the conditions with numerical examples, and to present a model of how DCCs could be applied with a toy problem in patient motion estimation with truncated projections.Methods:A mathematical derivation of the new parallel DCCs was performed by substituting the underlying imaging equation into the mathematical expression for the weighted backprojection and demonstrating the resulting polynomial form. This DCC result was extended to fanbeam projections by a substitution of parallel to fanbeam variables. Ideal fanbeam projections of a simple mathematical phantom were simulated and the DCCs for these projections were evaluated by fitting polynomials to the weighted backprojection. For the motion estimation problem, a parametrized motion was simulated using a dynamic version of the mathematical phantom, and both noiseless and noisy fanbeam projections were simulated for a full circular trajectory. The fanbeam DCCs were applied to extract the motion parameters, which allowed the motion contamination to be removed from the projections. A reconstruction was performed from the corrected projections.Results:The mathematical derivation revealed the anticipated polynomial behavior. The conversion to fanbeam variables led to a straight‐forward weighted fanbeam backprojection which yielded the same function and therefore the same polynomial behavior as occurred in the parallel case. Plots of the numerically calculated DCCs showed polynomial behavior visually indistinguishable from the fitted polynomials. For the motion estimation problem, the motion parameters were satisfactorily recovered and ten times more accurately for the noise‐free case. The reconstructed images showed that only a faint trace of the motion blur was still visible after correction from the noisy motion‐contaminated projections.Conclusions:New DCCs have been established for fanbeam and parallel projections, and these conditions have been validated using numerical experiments with truncated projections. It has been shown how these DCCs could be applied to extract parameters of unwanted physical effects in tomographic imaging, even with truncated projections.
Maximal Aerobic Capacity in the Winter-Olympics Endurance Disciplines: Olympic-Medal Benchmarks for the Time Period 1990–2013
Authors: Tønnessen Espen , Haugen Thomas A. , Hem Erlend , Leirstein Svein , Seiler Stephen 
Published: January 2015

Purpose:
To generate updated Olympic-medal benchmarks for V̇O2max in winter endurance disciplines, examine possible differences in V̇O2max between medalists and nonmedalists, and calculate gender difference in V̇O2max based on a homogeneous subset of world-leading endurance athletes.

Methods:
The authors identified 111 athletes who participated in winter Olympic Games/World Championships in the period 1990 to 2013. All identified athletes tested V̇O2max at the Norwegian Olympic Training Center within ±1 y of their championship performance. Testing procedures were consistent throughout the entire period.

Results:
For medal-winning athletes, the following relative V̇O2max values (mean:95% confidence intervals) for men/women were observed (mL · min–1 · kg–1): 84:87-81/72:77-68 for cross-country distance skiing, 78:81-75/68:73-64 for cross-country sprint skiing, 81:84-78/67:73-61 for biathlon, and 77:80-75 for Nordic combined (men only). Similar benchmarks for absolute V̇O2max (L/min) in male/female athletes are 6.4:6.1-6.7/4.3:4.1-4.5 for cross-country distance skiers, 6.3:5.8-6.8/4.0:3.7-4.3 for cross-country sprint skiers, 6.2:5.7-6.4/4.0:3.7-4.3 for biathletes, and 5.3:5.0-5.5 for Nordic combined (men only). The difference in relative V̇O2max between medalists and nonmedalists was large for Nordic combined, moderate for cross-country distance and biathlon, and small/trivial for the other disciplines. Corresponding differences in absolute V̇O2max were small/trivial for all disciplines. Male cross-country medalists achieve 15% higher relative V̇O2max than corresponding women.

Conclusions:
This study provides updated benchmark V̇O2max values for Olympic-medal-level performance in winter endurance disciplines and can serve as a guideline of the requirements for future elite athletes.
Evaluation of the Vitros Syphilis TPA Chemiluminescence Immunoassay as a First-Line Method for Reverse Syphilis Screening
Authors: González Victoria , Fernández Gema , Dopico Eva , Margall Nuria , Esperalba Juliana , Muñoz Carme , Castro Elisabeth , Sulleiro Elena , Matas Lurdes 
Published: January 2015

ABSTRACT
We report here the results of the diagnostic performances of Vitros Syphilis TPA (a chemiluminescence treponemal assay) compared with those of two treponemal enzyme immunoassays and of traditional versus reverse syphilis algorithms. Ease of use, automation, and high throughput make the Vitros Syphilis TPA assay a good choice for syphilis screening in high-volume laboratories.
A Pilot Evaluation of External Quality Assessment of GenoType MTBDR
plus
Versions 1 and 2 Using Dried Culture Spot Material
Authors: Gous N. , Isherwood L. E. , David A. , Stevens W. , Scott L. E. 
Published: January 2015

ABSTRACT

Dried culture spots (DCS) of inactivated
Mycobacteria strains
designed as part of an external quality assessment (EQA) program for the GeneXpert system has applications to other molecular tuberculosis (TB) diagnostic platforms. DCS tested on the GenoType MTBDR
plus
and
Mycobacterium
CM assays performed well with MTBDR
plus
version 2 but require increased bacterial concentration for use with version 1.
Use of the Optum Labs Data Warehouse To Assess Test Ordering Patterns for Diagnosis of Helicobacter pylori Infection in the United States
Authors: Theel Elitza S. , Johnson Ryan D. , Plumhoff Elizabeth , Hanson Curtis A. 
Published: January 2015

ABSTRACT

We surveyed national
Helicobacter pylori
diagnostic testing practices and diagnoses using commercial and Medicare medical claims data from Optum Labs (Cambridge, MA). Serologic testing for antibodies to
H. pylori
remains the most commonly ordered diagnostic test despite recent expert recommendations. Changes in reimbursement for serologic testing will likely drive future provider ordering practices.
Clinical Evaluation of the OneStep Gonorrhea RapiCard InstaTest for Detection of Neisseria gonorrhoeae in Symptomatic Patients from KwaZulu-Natal, South Africa
Authors: Abbai N. S. , Moodley P. , Reddy T. , Zondi T. G. , Rambaran S. , Naidoo K. , Ramjee G. 
Published: January 2015

ABSTRACT

We evaluated a point-of-care test for the detection of
Neisseria gonorrhoeae
in patients attending a public health clinic in KwaZulu-Natal, South Africa. The test showed a low sensitivity against PCR and culture (<40%); however, a higher specificity was observed (>95%). This test is unsuitable as a screening tool for gonorrhea.
Tom70 Mediates Sendai Virus-Induced Apoptosis on Mitochondria
Authors: Wei Bo , Cui Ye , Huang Yuefeng , Liu Heng , Li Lin , Li Mi , Ruan Kang-Cheng , Zhou Qin , Wang Chen 
Published: January 2015

ABSTRACT

Virus infection triggers immediate innate immune responses. Apoptosis represents another effective means to restrict virus invasion, besides robust expression of host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable for Sendai virus (SeV)-induced apoptosis, but the underlying mechanism is not fully understood. Here we report that a dynamic protein complex, Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis. The cytosolic proapoptotic protein Bax interacts specifically with IRF3 upon virus infection. The mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via Hsp90. Consequently, the relocation of Bax onto mitochondria induces the leakage of cytochrome
c
into the cytosol and initiates the corresponding apoptosis. Interestingly, IKK-i is essential for this apoptosis, whereas TBK1 is dispensable. Collectively, our study characterizes a novel protein complex that is important for SeV-induced apoptosis.

IMPORTANCE
Apoptosis is an effective means of sacrificing virus-infected cells and restraining the spread of virus. In this study, we demonstrate that IRF3 associates with Bax upon virus infection. Tom70 recruits this protein complex to the mitochondrial outer membrane through Hsp90, which thus induces the release of cytochrome
c
into the cytosol, initiating virus-induced apoptosis. Interestingly, IKK-i plays an essential role in this activation. This study uncovers a novel mechanism of SeV-induced apoptosis.
A Novel Humanized Antibody Neutralizes H5N1 Influenza Virus via Two Different Mechanisms
Authors: Tan Yunrui , Ng Qingyong , Jia Qiang , Kwang Jimmy , He Fang 
Published: January 2015

ABSTRACT
Highly pathogenic avian influenza virus subtype H5N1 continues to be a severe threat to public health, as well as the poultry industry, because of its high lethality and antigenic drift rate. Neutralizing monoclonal antibodies (MAbs) can serve as a useful tool for preventing, treating, and detecting H5N1. In the present study, humanized H5 antibody 8A8 was developed from a murine H5 MAb. Both the humanized and mouse MAbs presented positive activity in hemagglutination inhibition (HI), virus neutralization, and immunofluorescence assays against a wide range of H5N1 strains. Interestingly, both human and murine 8A8 antibodies were able to detect H5 in Western blot assays under reducing conditions. Further, by sequencing of escape mutants, the conformational epitope of 8A8 was found to be located within the receptor binding domain (RBD) of H5. The linear epitope of 8A8 was identified by Western blotting of overlapping fragments and substitution mutant forms of HA1. Reverse genetic H5N1 strains with individual mutations in either the conformational or the linear epitope were generated and characterized in a series of assays, including HI, postattachment, and cell-cell fusion inhibition assays. The results indicate that for 8A8, virus neutralization mediated by RBD blocking relies on the conformational epitope while binding to the linear epitope contributes to the neutralization by inhibiting membrane fusion. Taken together, the results of this study show that a novel humanized H5 MAb binds to two types of epitopes on HA, leading to virus neutralization via two mechanisms.

IMPORTANCE
Recurrence of the highly pathogenic avian influenza virus subtype H5N1 in humans and poultry continues to be a serious public health concern. Preventive and therapeutic measures against influenza A viruses have received much interest in the context of global efforts to combat the current and future pandemics. Passive immune therapy is considered to be the most effective and economically prudent preventive strategy against influenza virus besides vaccination. It is important to develop a humanized neutralizing monoclonal antibody (MAb) against all of the clades of H5N1. For the first time, we report in this study that a novel humanized H5 MAb binds to two types of epitopes on HA, leading to virus neutralization via two mechanisms. These findings further deepen our understanding of influenza virus neutralization.
A
trans
-Dominant Form of Gag Restricts Ty1 Retrotransposition and Mediates Copy Number Control
Authors: Saha Agniva , Mitchell Jessica A. , Nishida Yuri , Hildreth Jonathan E. , Ariberre Joshua A. , Gilbert Wendy V. , Garfinkel David J. 
Published: January 2015

ABSTRACT

Saccharomyces cerevisiae
and
Saccharomyces paradoxus
lack the conserved RNA interference pathway and utilize a novel form of copy number control (CNC) to inhibit Ty1 retrotransposition. Although noncoding transcripts have been implicated in CNC, here we present evidence that a truncated form of the Gag capsid protein (p22) or its processed form (p18) is necessary and sufficient for CNC and likely encoded by Ty1 internal transcripts. Coexpression of p22/p18 and Ty1 decreases mobility more than 30,000-fold. p22/p18 cofractionates with Ty1 virus-like particles (VLPs) and affects VLP yield, protein composition, and morphology. Although p22/p18 and Gag colocalize in the cytoplasm, p22/p18 disrupts sites used for VLP assembly. Glutathione
S
-transferase (GST) affinity pulldowns also suggest that p18 and Gag interact. Therefore, this intrinsic Gag-like restriction factor confers CNC by interfering with VLP assembly and function and expands the strategies used to limit retroelement propagation.

IMPORTANCE
Retrotransposons dominate the chromosomal landscape in many eukaryotes, can cause mutations by insertion or genome rearrangement, and are evolutionarily related to retroviruses such as HIV. Thus, understanding factors that limit transposition and retroviral replication is fundamentally important. The present work describes a retrotransposon-encoded restriction protein derived from the capsid gene of the yeast Ty1 element that disrupts virus-like particle assembly in a dose-dependent manner. This form of copy number control acts as a molecular rheostat, allowing high levels of retrotransposition when few Ty1 elements are present and inhibiting transposition as copy number increases. Thus, yeast and Ty1 have coevolved a form of copy number control that is beneficial to both “host and parasite.” To our knowledge, this is the first Gag-like retrotransposon restriction factor described in the literature and expands the ways in which restriction proteins modulate retroelement replication.
Phenotypic and Functional Characterization of Herpes Simplex Virus Glycoprotein B Epitope-Specific Effector and Memory CD8+T Cells from Symptomatic and Asymptomatic Individuals with Ocular Herpes
Authors: Khan Arif A. , Srivastava Ruchi , Spencer Doran , Garg Sumit , Fremgen Daniel , Vahed Hawa , Lopes Patricia P. , Pham Thanh T. , Hewett Charlie , Kuang Jasmine , Ong Nicolas , Huang Lei , Scarfone Vanessa M. , Nesburn Anthony B. , Wechsler Steven L. , BenMohamed Lbachir 
Published: January 2015

ABSTRACTHerpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8+T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8+T cells play a key role in the “natural” protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8+T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8+T cells (TEMcells) (CD45RAlowCCR7lowCD44highCD62Llow). In contrast, SYMP patients had frequent less-differentiated central memory CD8+T cells (TCMcells) (CD45RAlowCCR7highCD44lowCD62Lhigh). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8+T cells which responded mainly to gB342–350and gB561–569“ASYMP” epitopes, and simultaneously produced IFN-γ, CD107a/b, granzyme B, and perforin. In contrast, effector CD8+T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17–25and gB183–191“SYMP” epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with “ASYMP” CD8+TEMcell epitopes, but not with “SYMP” CD8+TCMcell epitopes, induced a strong CD8+T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8+TEMcells in protection against herpes and should be considered in the development of an effective vaccine.IMPORTANCEA significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8+T cells (TEMcells) (CD45RAlowCCR7lowCD44highCD62Llow) were found in healthy ASYMP individuals who are seropositive for HSV-1 but never had any recurrent herpetic disease, while there were frequent less-differentiated and monofunctional central memory CD8+T cells (TCMcells) (CD45RAlowCCR7highCD44lowCD62Lhigh) in SYMP patients. Immunization with “ASYMP” CD8+TEMcell epitopes, but not with “SYMP” CD8+TCMcell epitopes, induced a strong protective HSV-specific CD8+T cell response in HLA-A*02:01 transgenic mice. These findings are important for the development of a safe and effective T cell-based herpes vaccine.
Pharmacodynamic Imaging Guides Dosing of a Selective Estrogen Receptor Degrader
Authors: Heidari Pedram , Deng Francis , Esfahani Shadi A. , Leece Alicia K. , Shoup Timothy M. , Vasdev Neil , Mahmood Umar 
Published: January 2015

Abstract
Purpose: Estrogen receptor (ER) targeting is key in management of receptor-positive breast cancer. Currently, there are no methods to optimize anti-ER therapy dosing. This study assesses the use of 16α-18F-fluoroestradiol (18F-FES) PET for fulvestrant dose optimization in a preclinical ER+ breast cancer model.
Experimental Design: In vitro, 18F-FES retention was compared with ERα protein expression (ELISA) and ESR1 mRNA transcription (qPCR) in MCF7 cells (ER+) after treatment with different fulvestrant doses. MCF7 xenografts were grown in ovariectomized nude mice and assigned to vehicle, low- (0.05 mg), medium- (0.5 mg), or high-dose (5 mg) fulvestrant treatment groups (5–7 per group). Two and 3 days after fulvestrant treatment, PET/CT was performed using 18F-FES and 18F-FDG, respectively. ER expression was assessed by immunohistochemistry, ELISA, and qPCR on xenografts. Tumor proliferation was assessed using Ki67 immunohistochemistry.
Results: In vitro, we observed a parallel graded reduction in 18F-FES uptake and ER expression with increased fulvestrant doses, despite enhancement of ER mRNA transcription. In xenografts, ER expression significantly decreased with increased fulvestrant dose, despite similar mRNA expression and Ki67 staining among the treatment groups. We observed a significant dose-dependent reduction of 18F-FES PET mean standardized uptake value (SUVmean) with fulvestrant treatment but no significant difference among the treatment groups in 18F-FDG PET SUVmean.
Conclusions: We demonstrated that 18F-FES uptake mirrors the dose-dependent changes in functional ER expression with fulvestrant resulting in ER degradation and/or blockade; these precede changes in tumor metabolism and proliferation. Quantitative 18F-FES PET may be useful for tracking early efficacy of ER blockade/degradation and guiding ER-targeted therapy dosing in patients with breast cancer. Clin Cancer Res; 21(6); 1340–7. ©2015 AACR.