bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining Species-Specific Immunodominant B Cell Epitopes for Molecular Serology of Chlamydia Species
Authors: Rahman K. Shamsur , Chowdhury Erfan U. , Poudel Anil , Ruettger Anke , Sachse Konrad , Kaltenboeck Bernhard 
Published: March 2015

ABSTRACTUrgently needed species-specific enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies againstChlamydiaspp. have been elusive due to high cross-reactivity of chlamydial antigens. To identifyChlamydiaspecies-specific B cell epitopes for such assays, we ranked the potential epitopes of immunodominant chlamydial proteins that are polymorphic among allChlamydiaspecies. High-scoring peptides were synthesized with N-terminal biotin, followed by a serine-glycine-serine-glycine spacer, immobilized onto streptavidin-coated microtiter plates, and tested with mono-specific mouse hyperimmune sera against eachChlamydiaspecies in chemiluminescent ELISAs. For each of nineChlamydiaspecies, three to nine dominant polymorphic B cell epitope regions were identified on OmpA, CT618, PmpD, IncA, CT529, CT442, IncG, Omp2, TarP, and IncE proteins. Peptides corresponding to 16- to 40-amino-acid species-specific sequences of these epitopes reacted highly and with absolute specificity with homologous, but not heterologous,Chlamydiamonospecies-specific sera. Host-independent reactivity of such epitopes was confirmed by testing of sixC. pecorum-specific peptides from five proteins withC. pecorum-reactive sera from cattle, the natural host ofC. pecorum. The probability of cross-reactivity of peptide antigens from closely related chlamydial species or strains correlated with percent sequence identity and declined to zero at <50% sequence identity. Thus, phylograms of B cell epitope regions predict the specificity of peptide antigens for rational use in the genus-, species-, or serovar-specific molecular serology ofChlamydiaspp. We anticipate that these peptide antigens will improve chlamydial serology by providing easily accessible assays to nonspecialist laboratories. Our approach also lends itself to the identification of relevant epitopes of other microbial pathogens.
Immunogenicity and Efficacy of Flagellin-Envelope Fusion Dengue Vaccines in Mice and Monkeys
Authors: Liu Ge , Song Langzhou , Beasley David W. C. , Putnak Robert , Parent Jason , Misczak John , Li Hong , Reiserova Lucia , Liu Xiangyu , Tian Haijun , Liu Wenzhe , Labonte Darlene , Duan Lihua , Kim Youngsun , Travalent Linda , Wigington Devin , Weaver Bruce , Tussey Lynda 
Published: March 2015

ABSTRACTThe envelope (E) protein of flaviviruses includes three domains, EI, EII, and EIII, and is the major protective antigen. Because EIII is rich in type-specific and subcomplex-specific neutralizing epitopes and is easy to express, it is particularly attractive as a recombinant vaccine antigen. VaxInnate has developed a vaccine platform that genetically links vaccine antigens to bacterial flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue vaccines (TDVs) consisting of four constructs, each containing two copies of EIII fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus reduction neutralization test (FRNT50). In an immunogenicity study, rhesus macaques (n= 2) immunized subcutaneously with 10 μg or 90 μg of TDV three or four times, at 4- to 6-week intervals, developed neutralizing antibodies to four dengue virus (DENV) serotypes (mean post-dose 3 FRNT50titers of 102 to 601). In an efficacy study, rhesus macaques (n= 4) were immunized intramuscularly with 16 μg or 48 μg of TDV or a placebo control three times, at 1-month intervals. The animals that received 48-μg doses of TDV developed neutralizing antibodies against the four serotypes (geometric mean titers of 49 to 258) and exhibited reduced viremia after DENV-2 challenge, with a group mean viremia duration of 1.25 days and 2 of 4 animals being completely protected, compared to the placebo-treated animals, which all developed viremia, with a mean duration of 4 days. In conclusion, flagellin-EIII fusion vaccines are immunogenic and partially protective in a nonhuman primate model.
Fever in a Visitor to Canada: a Case of Mistaken Identity
Authors: Warren Thomas , Lau Rachel , Ralevski Filip , Rau Neil , Boggild Andrea K. 
Published: March 2015

ABSTRACT

We report a case of babesiosis in a traveler from India who was diagnosed with malaria on the basis of blood smears. Pan-
Plasmodium
PCR was positive, though species-specific assays were negative. Reexamination of blood smears and
Babesia
-specific PCR confirmed babesiosis. We highlight the overlapping clinical and diagnostic features of malaria and babesiosis and the potential cross-reactivity of
Plasmodium
primers in cases of babesiosis.
A Novel Technique for Detecting Antibiotic-Resistant Typhoid from Rapid Diagnostic Tests
Authors: Nic Fhogartaigh Caoimhe , Dance David A. B. , Davong Viengmon , Tann Pisey , Phetsouvanh Rattanaphone , Turner Paul , Dittrich Sabine , Newton Paul N. 
Published: March 2015

ABSTRACT

Fluoroquinolone-resistant typhoid is increasing. An antigen-detecting rapid diagnotic test (RDT) can rapidly diagnose typhoid from blood cultures. A simple, inexpensive molecular technique performed with DNA from positive RDTs accurately identified
gyrA
mutations consistent with phenotypic susceptibility testing results. Field diagnosis combined with centralized molecular resistance testing could improve typhoid management and surveillance in low-resource settings.
Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression
Authors: Dlugolenski Daniel , Jones Les , Howerth Elizabeth , Wentworth David , Tompkins S. Mark , Tripp Ralph A. 
Published: March 2015

ABSTRACT
Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression.

IMPORTANCE
Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.
The Road Less Traveled: HIV's Use of Alternative Routes through Cellular Pathways
Authors: Marx Ailie , Alian Akram 
Published: March 2015

ABSTRACT
Pathogens such as HIV-1, with their minimalist genomes, must navigate cellular networks and rely on hijacking and manipulating the host machinery for successful replication. Limited overlap of host factors identified as vital for pathogen replication may be explained by considering that pathogens target, rather than specific cellular factors, crucial cellular pathways by targeting different, functionally equivalent, protein-protein interactions within that pathway. The ability to utilize alternative routes through cellular pathways may be essential for pathogen survival when restricted and provide flexibility depending on the viral replication stage and the environment in the infected host. In this minireview, we evaluate evidence supporting this notion, discuss specific HIV-1 examples, and consider the molecular mechanisms which allow pathogens to flexibly exploit different routes.
Evidence-based development of a post-surgical lumbar discectomy leaflet intervention: a Delphi consensus study
Authors: Goodwin P C , Wright C C , Allan C , Crowther L , Darley C , Heap A , Paul E , White L , Rushton A 
Published: March 2015

ObjectiveTo produce free, expert-informed postoperative information for lumbar discectomy patients, satisfying UK National Health Service Information Standards.DesignA mixed methods approach utilising the Delphi technique and focus groups.SettingFive spinal centres across the UK.ParticipantsPanel members included 23 physiotherapists, 11 patients and 17 spinal surgeons.InterventionThree rounds of questionnaires including open and closed questions and attendance at a clinician/patient focus group.ResultsResponse rates of 85%, 26% and 35% were achieved for the Delphi rounds. Ten clinicians and six patients participated in the focus groups. Consensus for leaflet sections was achieved in round 1 and content in round 3. The focus groups informed further revisions.ConclusionsA consensually agreed, Information Standard compliant, patient lumbar discectomy leaflet was produced containing: (1) normal spine anatomy; (2) anatomy disc herniation and surgery; (3) back protection strategies and (4) frequently asked questions. Illustrations of exercises enable tailoring to the individual patient.
Population Movement and Sudden Cardiac Arrest Location
Authors: Marijon Eloi , Bougouin Wulfran , Tafflet Muriel , Karam Nicole , Jost Daniel , Lamhaut Lionel , Beganton Frankie , Pelloux Patricia , Degrange Hervé , Béal Guillaume , Tourtier Jean-Pierre , Hagège Albert A. , Le Heuzey Jean-Yves , Desnos Michel , Dumas Florence , Spaulding Christian , Celermajer David S. , Cariou Alain , Jouven Xavier 
Published: March 2015

Background—
Although the benefits of automatic external defibrillators are undeniable, their effectiveness could be dramatically improved. One of the key issues is the disparity between the locations of automatic external defibrillators and sudden cardiac arrests (SCAs).

Methods and Results—

From emergency medical services and other Parisian agencies, data on all SCAs occurring in public places in Paris, France, were prospectively collected between 2000 and 2010 and recorded using 2020 grid areas. For each area, population density, population movements, and landmarks were analyzed. Of the 4176 SCAs, 1255 (30%) occurred in public areas, with a highly clustered distribution of SCAs, especially in areas containing major train stations (12% of SCAs in 0.75% of the Paris area). The association with population density was poor, with a nonsignificant increase in SCAs with population density (
P
=0.4). Occurrence of public SCAs was, in contrast, highly associated with population movements (
P
<0.001). In multivariate analysis including other landmarks in each grid cell in the model and demographic characteristics, population movement remained significantly associated with the occurrence of SCA (odds ratio, 1.48; 95% confidence interval, 1.34–1.63;
P
<0.0001), as well as grid cells containing train stations (odds ratio, 3.80; 95% confidence interval, 2.66–5.36;
P
<0.0001).

Conclusions—
Using a systematic analysis of determinants of SCA in public places, we demonstrated the extent to which population movements influence SCA distribution. Our findings also suggested that beyond this key risk factor, some areas are dramatically associated with a higher risk of SCA.
Lagrangian Analyses of Rainfall Structure and Evolution for Organized Thunderstorm Systems in the Urban Corridor of the Northeastern United States
Authors: Yeung June K. , Smith James A. , Baeck Mary Lynn , Villarini Gabriele 
Published: March 2015

AbstractIn this study, a climatology of the structure and evolution of rainfall for organized thunderstorm systems in the urban corridor of the northeastern United States is developed. These storm systems are major agents of flash flooding for urban regions of the northeastern United States and, more generally, for the United States east of the Rocky Mountains. The analyses are motivated by problems that center on characterizing flash flood hazards. The authors focus on spatial heterogeneities of rainfall associated with urbanization in a region of complex landscape including mountainous terrain and land–water boundaries along the geometrically complex coastline of the New York City–New Jersey metropolitan region. The sample of storms selected for investigation consists of the 50 days from April to September 2001–09 with the largest cloud-to-ground lightning flash density derived from National Lightning Detection Network (NLDN) observations over the study region. Storm-tracking analyses of 3D radar reflectivity fields are performed for the 50 storm days and used to develop a Lagrangian climatology of storm structure and evolution for the study region. Rainfall analyses for the 50 storm days are based on high-resolution (1 km, 15 min) bias-corrected radar rainfall fields developed from the Hydro-NEXRAD system. The analyses suggest that complex terrain and land–water boundaries have large impacts on Lagrangian storm properties. Areas of increased heavy rainfall and lightning flash density over New York City were identified. The authors found evidence for changing storm structure as thunderstorms pass over New York City, but little evidence that thunderstorms split as they approach New York City.
Bjerknes-like Compensation in the Wintertime North Pacific
Authors: Bishop Stuart P. , Bryan Frank O. , Small R. Justin 
Published: March 2015

AbstractObservational and model evidence has been mounting that mesoscale eddies play an important role in air–sea interaction in the vicinity of western boundary currents and can affect the jet stream storm track. What is less clear is the interplay between oceanic and atmospheric meridional heat transport in the vicinity of western boundary currents. It is first shown that variability in the North Pacific, particularly in the Kuroshio Extension region, simulated by a high-resolution fully coupled version of the Community Earth System Model matches observations with similar mechanisms and phase relationships involved in the variability. The Pacific decadal oscillation (PDO) is correlated with sea surface height anomalies generated in the central Pacific that propagate west preceding Kuroshio Extension variability with a ~3–4-yr lag. It is then shown that there is a near compensation of O(0.1) PW (PW ≡ 1015 W) between wintertime atmospheric and oceanic meridional heat transport on decadal time scales in the North Pacific. This compensation has characteristics of Bjerknes compensation and is tied to the mesoscale eddy activity in the Kuroshio Extension region.
Effect of coculturing canine notochordal, nucleus pulposus and mesenchymal stromal cells for intervertebral disc regeneration
Authors: Arkesteijn Irene TM , Smolders Lucas A , Spillekom Sandra , Riemers Frank M , Potier Esther , Meij Björn P , Ito Keita , Tryfonidou Marianna A 
Published: March 2015

Abstract
Introduction
Early degenerative changes in the nucleus pulposus (NP) are observed after the disappearance of notochordal cells (NCs). Thus, it has been suggested that NCs play an important role in maintaining the NP and may have a regenerative potential on other cells of the NP. As the number of resident NP cells (NPCs) decreases in a degenerating disc, mesenchymal stromal (stem) cells (MSCs) may be used for cell supplementation. In this study, using cells of one species, the regenerative potential of canine NCs was assessed in long-term three-dimensional coculture with canine NPCs or MSCs.

Methods
Canine NCs and canine NPCs or MSCs were cocultured in alginate beads for 28 days under hypoxic and high-osmolarity conditions. Cell viability, cell morphology and DNA content, extracellular matrix production and expression of genes related to NC markers (Brachyury, KRT18) and NP matrix production (ACAN, COL2A1, COL1A1) were assessed after 1, 15 and 28 days of culture.

Results
NCs did not completely maintain their phenotype (morphology, matrix production, gene expression) during 28 days of culture. In cocultures of NPCs and NCs, both extracellular matrix content and anabolic gene expression remained unchanged compared with monoculture groups, whereas cocultures of MSCs and NCs showed increased glycosaminoglycan/DNA. However, the deposition of these proteoglycans was observed near the NCs and not the MSCs. Brachyury expression in the MSC and NC coculture group increased in time. The latter two findings indicate a trophic effect of MSCs on NCs rather than vice versa.

Conclusions
No regenerative potential of canine NCs on canine NPCs or MSCs was observed in this study. However, significant changes in NC phenotype in long-term culture may have resulted in a suboptimal regenerative potential of these NCs. In this respect, NC-conditioned medium may be better than coculture for future studies of the regenerative potential of NCs.
Thymic stromal lymphopoietin in hepatitis C virus-related cryoglobulinemic vasculitis: gene expression level and protein distribution
Authors: Sansonno Domenico , Russi Sabino , Sansonno Silvia , Pavone Fabio , Dammacco Franco 
Published: March 2015

Abstract
Introduction
Hepatitis C virus (HCV) infection can be detected in virtually all patients with cryoglobulinemic vasculitis (CV). Among its many effects, the virus is able to stimulate the production of thymic stromal lymphopoietin (TSLP) by infected hepatocytes. In this study, we assessed the systemic levels and tissue distribution of TSLP in 60 chronically HCV-infected patients, 36 with and 24 without CV.

Methods
Serum TSLP levels were measured by an enzyme-linked immunosorbent assay (ELISA) method. TSLP mRNA was assessed in patient samples by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). TSLP protein in liver and skin biopsy samples was revealed by indirect immunofluorescence. All other methods were carried out according to standardized procedures.

Results
Serum TSLP levels were significantly higher in patients with than in those without CV and in healthy individuals. Higher TSLP levels paralleled specific mRNA expression and the up-regulation of TSLP protein in liver tissue. Compared with non-CV patients, higher TSLP levels in CV were accompanied by a higher frequency of circulating mono/oligoclonal B-cell expansions (8% vs. 92%, p < 0.0001) and a higher number of peripheral CD20+ B-cells (10.3% vs. 15.5% p = 0.04). In addition, TSLP mRNA expression in the liver of CV patients was lower than in their correspondent skin tissue and paralleled specific immune deposits of TSLP protein in keratinocytes.

Conclusion
Overall, this study shows that TSLP secreted by hepatocytes and keratinocytes of HCV-infected patients with CV is involved in the pathogenesis of vasculitis and may possibly support the therapeutic use of TSLP-targeted monoclonal antibodies.
Challenges in identifying the best source of stem cells for cardiac regeneration therapy
Authors: Dixit Parul , Katare Rajesh 
Published: March 2015

AbstractThe overall clinical cardiac regeneration experience suggests that stem cell therapy can be safely performed, but it also underlines the need for reproducible results for their effective use in a real-world scenario. One of the significant challenges is the identification and selection of the best suited stem cell type for regeneration therapy. Bone marrow mononuclear cells, bone marrow-derived mesenchymal stem cells, resident or endogenous cardiac stem cells, endothelial progenitor cells and induced pluripotent stem cells are some of the stem cell types which have been extensively tested for their ability to regenerate the lost myocardium. While most of these cell types are being evaluated in clinical trials for their safety and efficacy, results show significant heterogeneity in terms of efficacy. The enthusiasm surrounding regenerative medicine in the heart has been dampened by the reports of poor survival, proliferation, engraftment, and differentiation of the transplanted cells. Therefore, the primary challenge is to create clearcut evidence on what actually drives the improvement of cardiac function after the administration of stem cells. In this review, we provide an overview of different types of stem cells currently being considered for cardiac regeneration and discuss why associated factors such as practicality and difficulty in cell collection should also be considered when selecting the stem cells for transplantation. Next, we discuss how the experimental variables (type of disease, marker-based selection and use of different isolation techniques) can influence the study outcome. Finally, we provide an outline of the molecular and genetic approaches to increase the functional ability of stem cells before and after transplantation.
Culture of human mesenchymal stem cells using a candidate pharmaceutical grade xeno-free cell culture supplement derived from industrial human plasma pools
Authors: Díez José M , Bauman Ewa , Gajardo Rodrigo , Jorquera Juan I 
Published: March 2015

Abstract
Introduction
Fetal bovine serum (FBS) is an animal product used as a medium supplement. The animal origin of FBS is a concern if cultured stem cells are to be utilized for human cell therapy. Therefore, a substitute for FBS is desirable. In this study, an industrial, xeno-free, pharmaceutical-grade supplement for cell culture (SCC) under development at Grifols was tested for growth of human mesenchymal stem cells (hMSCs), cell characterization, and differentiation capacity.

Methods
SCC is a freeze-dried product obtained through cold-ethanol fractionation of industrial human plasma pools from healthy donors. Bone marrow-derived hMSC cell lines were obtained from two commercial suppliers. Cell growth was evaluated by culturing hMSCs with commercial media or media supplemented with SCC or FBS. Cell viability and cell yield were assessed with an automated cell counter. Cell surface markers were studied by indirect immunofluorescence assay. Cells were cultured then differentiated into adipocytes, chondrocytes, osteoblasts, and neurons, as assessed by specific staining and microscopy observation.

Results
SCC supported the growth of commercial hMSCs. Starting from the same number of seeded cells in two consecutive passages of culture with medium supplemented with SCC, hMSC yield and cell population doubling time were equivalent to the values obtained with the commercial medium and was consistent among lots. The viability of hMSCs was higher than 90%, while maintaining the characteristic phenotype of undifferentiated hMSCs (positive for CD29, CD44, CD90, CD105, CD146, CD166 and Stro-1; negative for CD14 and CD19). Cultured hMSCs maintained the potential for differentiation into adipocytes, chondrocytes, osteoblasts, and neurons.

Conclusions
The tested human plasma-derived SCC sustains the adequate growth of hMSCs, while preserving their differentiation capacity. SCC can be a potential candidate for cell culture supplement in advanced cell therapies.