bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers for differentiation of causes of respiratory distress in dogs and cats: Part 1 – Cardiac diseases and pulmonary hypertension
Authors: Smith Katherine F. , Quinn Rebecca L. , Rahilly Louisa J. 
Published: June 2015

AbstractObjectiveTo review the current veterinary and relevant human literature regarding biomarkers of cardiac disease leading to respiratory compromise.Data SourcesVeterinary and human medical literature: original research articles, scientific reviews, consensus statements, and recent textbooks.Human Data SynthesisCardiac troponins (cTn) and natriuretic peptides are routinely used in human medicine.Veterinary Data SynthesisAlthough biomarkers should not be accepted in lieu of gold standard diagnostics, they may be useful in directing care in the stabilization process. Biomarkers of congestive heart failure (CHF) include natriuretic peptides, cTn, and endothelin. cTnI is useful in differentiating causes of pericardial effusion, but is unlikely to be useful in differentiating CHF from other causes of respiratory distress. The most extensively studied and promising cardiac biomarker is amino‐terminal probrain natriuretic peptide, although a bedside test is not currently available. Other natriuretic peptides have also proven useful, but have lower availability. Endothelin is unlikely to be clinically useful. Although critically evaluated for their use in cardiac diseases, many of the biomarkers are affected by more than one type of respiratory or systemic disease. Several cardiac biomarkers are increased in cases of pulmonary hypertension (PH), but discerning CHF alone from PH or a combination of heart disease and PH is challenging when evaluating biomarkers alone.ConclusionAt this time, there are no point‐of‐care tests for biomarkers that can reliably differentiate among causes of dyspnea of cardiac origin in dogs and cats, although there are reference laboratory tests that show promise and future development of point‐of‐care tests that may be useful in certain situations.
T‐cell subsets in autologous and allogeneic peripheral blood stem cell concentrates
Authors: Strobel J. , Moellmer I. , Zingsem J. , Hauck‐Dlimi B. , Eckstein R. , Strasser E. 
Published: June 2015

Background and ObjectivesRegulatory T cells (Tregs) and other T‐cell subsets are of importance in the setting of autologous and allogeneic stem cell transplantations. We conducted a study to assess the content of peripheral blood stem cell concentrates and related apheresis parameters in the autologous and allogeneic setting.Material and MethodsWe characterized 53 donors, patients and peripheral blood stem cell concentrates (PBSC) regarding the content of CD45+ cells, lymphocytes, CD3+ cells, CD3+ CD4+ T cells, CD3+ CD4+ CD25+ T cells, CD3+ CD4+ CD25+ CD127low/negative Tregs and CD34+ cells and calculated cell yields, recruitment factors and collection efficiency for all cell types. We compared allogeneic data with autologous data.ResultsAutologous PBSC show significantly lower concentrations of T‐cell subsets compared to allogeneic PBSC (17 112/μl CD4+, 14 858/μl CD4+ CD25+ and 1579/μl CD3+ CD4+ CD25+ CD127low/negative Tregs in autologous compared to 65 539/μl CD4+, 44 208+/μl CD4+ CD25+ and 5040/μl CD3+ CD4+ CD25+ CD127low/negative Tregs in allogeneic PBSC, respectively), in contrast to CD34+ concentrations (5342/μl CD34+ in autologous compared to 2367/μl CD34+ in allogeneic PBSC, respectively). Accordantly, all T‐cell yields are lower in the autologous setting compared to allogeneic PBSC. However, recruitment factor and collection efficiency of all cell types are higher in autologous compared to allogeneic PBSC, but not all parameters differ significantly when groups are compared.ConclusionT‐cell subsets and especially Tregs are a substantial part of PBSC transplantation, as considerable recruitment during apheresis occurs. In large volume apheresis, the collection efficiency of Treg is comparable to that of CD34+ cells, while recruitment factors are even higher.
Effect of sludge retention time on inclined plate function, treatment performance and sludge characteristics of inclined plate membrane bioreactors treating municipal wastewater
Authors: Ittisupornrat Suda , Tobino Tomohiro , Yamamoto Kazuo 
Published: June 2015

AbstractTwo identical bench scale inclined plate membrane bioreactors (ip‐MBRs) were operated for the treatment of real municipal wastewater for 1 year. Sludge retention time (SRT) was varied over the course of operation to investigate the effects on inclined plate function, treatment performance and sludge characteristic. Removal rates of chemical oxygen demand and ammonia over 90% and of total nitrogen (TN) more than 70% were achieved when ip‐MBRs were operated under SRTs between infinite and 40 days while short SRT (20 days) negatively affected TN removal. When the sludge concentration in anoxic tank exceeded 15 g/L, the failure of the inclined plate function was observed, resulting in no difference in sludge concentrations between aerobic and anoxic tanks. To avoid severe effects on inclined plate function and treatment performance, an SRT range of 40–80 days was recommended for ip‐MBRs. Moreover, sludge floc size under prolonged SRT became smaller than that under short SRT due to increased attrition among the sludge floc particles caused by strong aeration needed for keeping a sufficient dissolved oxygen level.
Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep
Authors: Miller Myrna M. , Bennett Kristine E. , Drolet Barbara S. , Lindsay Robbin , Mecham James O. , Reeves Will K. , Weingartl Hana M. , Wilson William C. 
Published: June 2015

ABSTRACTRift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. In North America, there are susceptible ruminant hosts and competent mosquito vectors, yet there are no fully licensed animal vaccines for this arthropod-borne virus, should it be introduced. Studies in sheep and cattle have found the attenuated strain of RVFV, MP-12, to be both safe and efficacious based on early testing, and a 2-year conditional license for use in U.S. livestock has been issued. The purpose of this study was to further determine the vaccine's potential to infect mosquitoes, the duration of humoral immunity to 24 months postvaccination, and the ability to prevent disease and viremia from a virulent challenge. Vaccination experiments conducted in sheep found no evidence of a potential for vector transmission to 4 North American mosquito species. Neutralizing antibodies were elicited, with titers of >1:40 still present at 24 months postvaccination. Vaccinates were protected from clinical signs and detectable viremia after challenge with virulent virus, while control sheep had fever and high-titered viremia extending for 5 days. Antibodies to three viral proteins (nucleocapsid N, the N-terminal half of glycoprotein GN, and the nonstructural protein from the short segment NSs) were also detected to 24 months using competitive enzyme-linked immunosorbent assays. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates protective immunity to a virulent challenge with antibody duration of at least 2 years, with no evidence of a risk for vector transmission.
Does the Presence of Scrapie Affect the Ability of Current Statutory Discriminatory Tests To Detect the Presence of Bovine Spongiform Encephalopathy?
Authors: Simmons M. M. , Chaplin M. J. , Vickery C. M. , Simon S. , Davis L. , Denyer M. , Lockey R. , Stack M. J. , O'Connor M. J. , Bishop K. , Gough K. C. , Maddison B. C. , Thorne L. , Spiropoulos J. 
Published: June 2015

ABSTRACT

Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new
in vitro
discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE.
Potential Pathogenetic Role of Bovine Herpesvirus 4 in Two Dairy Cows with Dermatitis-Pyrexia-Hemorrhagic Syndrome
Authors: Bellino Claudio , Iussich Selina , Biasato Ilaria , Peletto Simone , Caruso Claudio , Gianella Paola , Cagnasso Aurelio , D'Angelo Antonio 
Published: June 2015

ABSTRACT
Dermatitis, pyrexia, and hemorrhagic syndrome (DPHS) is a rare bovine syndrome of unclear etiology. We describe two DPHS cases, the first to occur in Italy, with clinicopathological findings suggesting a potential pathogenetic role of bovine herpesvirus-4 (BoHV-4).
β-
d
-Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Koltze Antonia , Rath Peter , Schöning Stefan , Steinmann Jörg , Wichelhaus Thomas A. , Bader Peter , Bochennek Konrad , Lehrnbecher Thomas 
Published: June 2015

ABSTRACT

While the assessment of β-
d
-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and
Candida
sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness.
Intracellular Transport of Vaccinia Virus in HeLa Cells Requires WASH-VPEF/FAM21-Retromer Complexes and Recycling Molecules Rab11 and Rab22
Authors: Hsiao Jye-Chian , Chu Li-Wei , Lo Yung-Tsun , Lee Sue-Ping , Chen Tzu-Jung , Huang Cheng-Yen , Ping Yueh-Hsin , Chang Wen 
Published: June 2015

ABSTRACT

Vaccinia virus, the prototype of the
Orthopoxvirus
genus in the family
Poxviridae
, infects a wide range of cell lines and animals. Vaccinia mature virus particles of the WR strain reportedly enter HeLa cells through fluid-phase endocytosis. However, the intracellular trafficking process of the vaccinia mature virus between cellular uptake and membrane fusion remains unknown. We used live imaging of single virus particles with a combination of various cellular vesicle markers, to track fluorescent vaccinia mature virus particle movement in cells. Furthermore, we performed functional interference assays to perturb distinct vesicle trafficking processes in order to delineate the specific route undertaken by vaccinia mature virus prior to membrane fusion and virus core uncoating in cells. Our results showed that vaccinia virus traffics to early endosomes, where recycling endosome markers Rab11 and Rab22 are recruited to participate in subsequent virus trafficking prior to virus core uncoating in the cytoplasm. Furthermore, we identified WASH-VPEF/FAM21-retromer complexes that mediate endosome fission and sorting of virus-containing vesicles prior to virus core uncoating in the cytoplasm.

IMPORTANCE
Vaccinia mature virions of the WR strain enter HeLa cells through fluid phase endocytosis. We previously demonstrated that virus-containing vesicles are internalized into phosphatidylinositol 3-phosphate
positive macropinosomes, which are then fused with Rab5-positive early endosomes. However, the subsequent process of sorting the virion-containing vesicles prior to membrane fusion remains unclear. We dissected the intracellular trafficking pathway of vaccinia mature virions in cells up to virus core uncoating in cytoplasm. We show that vaccinia mature virions first travel to early endosomes. Subsequent trafficking events require the important endosome-tethered protein VPEF/FAM21, which recruits WASH and retromer protein complexes to the endosome. There, the complex executes endosomal membrane fission and cargo sorting to the Rab11-positive and Rab22-positive recycling pathway, resulting in membrane fusion and virus core uncoating in the cytoplasm.
Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8+T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses
Authors: Zhang Shihong , Bakshi Rakesh K. , Suneetha Pothakamuri Venkata , Fytili Paraskevi , Antunes Dinler A. , Vieira Gustavo F. , Jacobs Roland , Klade Christoph S. , Manns Michael P. , Kraft Anke R. M. , Wedemeyer Heiner , Schlaphoff Verena , Cornberg Markus 
Published: June 2015

ABSTRACTT cell responses play a critical role in controlling or clearing viruses. Therefore, strategies to prevent or treat infections include boosting T cell responses. T cells specific for various pathogens have been reported in unexposed individuals and an influence of such cells on the response toward vaccines is conceivable. However, little is known about their frequency, repertoire, and impact on vaccination. We performed a detailed characterization of CD8+T cells specific to a hepatitis C virus (HCV) epitope (NS3-1073) in 121 HCV-seronegative individuals. We show thatin vitroHCV NS3-1073-specific CD8+T cell responses were rather abundantly detectable in one-third of HCV-seronegative individuals irrespective of risk factors for HCV exposure.Ex vivo, these NS3-1073-specific CD8+T cells were found to be both naive and memory cells. Importantly, recognition of various peptides derived from unrelated viruses by NS3-1073-specific CD8+T cells showed a considerable degree of T cell cross-reactivity, suggesting that they might in part originate from previous heterologous infections. Finally, we further provide evidence that preexisting NS3-1073-specific CD8+T cells can impact the T cell response toward peptide vaccination. Healthy, vaccinated individuals who showed anin vitroresponse toward NS3-1073 already before vaccination displayed a more vigorous and earlier response toward the vaccine.IMPORTANCEPreventive and therapeutic vaccines are being developed for many viral infections and often aim on inducing T cell responses. Despite effective antiviral drugs against HCV, there is still a need for a preventive vaccine. However, the responses to vaccines can be highly variable among different individuals. Preexisting T cells in unexposed individuals could be one reason that helps to explain the variable T cell responses to vaccines. Based on our findings, we suggest that HCV CD8+T cells are abundant in HCV-seronegative individuals but that their repertoire is highly diverse due to the involvement of both naive precursors and cross-reactive memory cells of different specificities, which can influence the response to vaccines. The data may emphasize the need to personalize immune-based therapies based on the individual's T cell repertoire that is present before the immune intervention.
H3K27 Demethylation at the Proviral Promoter Sensitizes Latent HIV to the Effects of Vorinostat in
Ex Vivo
Cultures of Resting CD4
+
T Cells
Authors: Tripathy Manoj K. , McManamy Mary E. M. , Burch Brandon D. , Archin Nancie M. , Margolis David M. 
Published: June 2015

ABSTRACT

Histone methyltransferase inhibitors (HMTis) and histone deacetylase inhibitors (HDACis) are reported to synergistically induce the expression of latent human immunodeficiency virus type 1 (HIV-1), but studies have largely been performed with cell lines. As specific and potent HMTis directed at EZH1 (enhancer of zeste 2 Polycomb repressive complex 2 subunit 1)/EZH2 are now in human testing, we wished to rigorously test such an inhibitor in a primary resting T-cell model of HIV latency. We found that GSK343, a potent and selective EZH2/EZH1 inhibitor, reduced trimethylation of histone 3 at lysine 27 (H3K27) of the HIV provirus in resting cells. Remarkably, this epigenetic change was not associated with increased proviral expression in latently infected resting cells. However, following the reduction in H3K27 at the HIV long terminal repeat (LTR), subsequent exposure to the HDACi suberoylanilide hydroxamic acid or vorinostat (VOR) resulted in increases in HIV
gag
RNA and HIV p24 antigen production that were up to 2.5-fold greater than those induced by VOR alone. Therefore, in primary resting CD4
+
T cells, true mechanistic synergy in the reversal of HIV latency may be achieved by the combination of HMTis and HDACis. Although other cellular effects of EZH2 inhibition may contribute to the sensitization of the HIV LTR to subsequent exposure to VOR, and to increase viral antigen production, this synergistic effect is directly associated with H3K27 demethylation at nucleosome 1 (Nuc-1). Based upon our findings, the combination of HMTis and HDACis should be considered for testing in animal models or clinical trials.

IMPORTANCE
Demethylation of H3K27 mediated by the histone methyltransferase inhibitor GSK343 in primary resting T cells is slow, occurring over 96 h, but by itself does not result in a significant upregulation of cell-associated HIV RNA expression or viral antigen production. However, following H3K27 demethylation, latent viral expression within infected primary resting CD4
+
T cells is synergistically increased upon exposure to the histone deacetylase inhibitor vorinostat. Demethylation at H3K27 sensitizes the HIV promoter to the effects of an HDACi and provides a proof-of-concept for the testing of combination epigenetic approaches to disrupt latent HIV infection, a necessary step toward the eradication of HIV infection.
Inhibition of O-Linked
N
-Acetylglucosamine Transferase Reduces Replication of Herpes Simplex Virus and Human Cytomegalovirus
Authors: Angelova Magdalena , Ortiz-Meoz Rodrigo F. , Walker Suzanne , Knipe David M. 
Published: June 2015

ABSTRACT

O-linked
N
-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential cellular enzyme that posttranslationally modifies nuclear and cytoplasmic proteins via O-linked addition of a single
N
-acetylglucosamine (GlcNAc) moiety. Among the many targets of OGT is host cell factor 1 (HCF-1), a transcriptional regulator that is required for transactivation of the immediate-early genes of herpes simplex virus (HSV). HCF-1 is synthesized as a large precursor that is proteolytically cleaved by OGT, which may regulate its biological function. In this study, we tested whether inhibition of the enzymatic activity of OGT with a small molecule inhibitor, OSMI-1, affects initiation of HSV immediate-early gene expression and viral replication. We found that inhibiting OGT's enzymatic activity significantly decreased HSV replication. The major effect of the inhibitor occurred late in the viral replication cycle, when it reduced the levels of late proteins and inhibited capsid formation. However, depleting OGT levels with small interfering RNA (siRNA) reduced the expression of HSV immediate-early genes, in addition to reducing viral yields. In this study, we identified OGT as a novel cellular factor involved in HSV replication. Our results obtained using a small molecule inhibitor and siRNA depletion suggest that OGT's glycosylation and scaffolding functions play distinct roles in the replication cycle of HSV.

IMPORTANCE
Antiviral agents can target viral or host gene products essential for viral replication. O-GlcNAc transferase (OGT) is an important cellular enzyme that catalyzes the posttranslational addition of GlcNAc sugar residues to hundreds of nuclear and cytoplasmic proteins, and this modification regulates their activity and function. Some of the known OGT targets are cellular proteins that are critical for the expression of herpes simplex virus (HSV) genes, suggesting a role for OGT in the replication cycle of HSV. In this study, we found that OGT is required for efficient expression of viral genes and for assembly of new virions. Thus, we identify OGT as a novel host factor involved in the replication of HSV and a potential target for antiviral therapy.
Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease
Authors: Hepojoki J. , Salmenperä P. , Sironen T. , Hetzel U. , Korzyukov Y. , Kipar A. , Vapalahti O. 
Published: June 2015

ABSTRACT

Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus
Reptarenavirus
within the family
Arenaviridae
. We used next-generation sequencing and
de novo
sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus.