bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi‐Institutional Study Evaluating the Diagnostic Utility of the Spec cPL™and SNAP® cPL™in Clinical Acute Pancreatitis in 84 Dogs
Authors: McCord K. , Morley P.S. , Armstrong J. , Simpson K. , Rishniw M. , Forman M.A. , Biller D. , Parnell N. , Arnell K. , Hill S. , Avgeris S. , Gittelman H. , Moore M. , Hitt M. , Oswald G. , Marks S. , Burney D. , Twedt D. 
Published: June 2012

BackgroundPancreas‐specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically.Hypothesis/ObjectivesTo describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic‐specific lipase immunoassays, SpeccPL(SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase.AnimalsA total of 84 dogs; 27 withoutAPand 57 with clinical signs associated withAP.MethodsMulticenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinicalAPby a consensus of experts blinded toSPECandSNAPresults. Bayesian latent class analyses were used to estimate the diagnostic accuracy ofSPECandSNAP.ResultsThe estimates for test sensitivities and specificities, respectively, ranged between 91.5–94.1% and 71.1–77.5% forSNAP, 86.5–93.6% and 66.3–77.0% forSPEC(cutoff value of 200 μg/L), 71.7–77.8% and 80.5–88.0% forSPEC(cutoff value of 400 μg/L), and were 52.4–56.0% and 76.7–80.6% for amylase, and 43.4–53.6% and 89.3–92.5% for lipase.Conclusions and Clinical ImportanceSNAPandSPEChave higher sensitivity for diagnosing clinicalAPthan does measurement of serum amylase or lipase activity. A positiveSPECorSNAPhas a good positive predictive value (PPV) in populations likely to haveAPand a good negative predictive value (NPV) when there is low prevalence of disease.
M‐type potassium channels modulate Schaffer collateral–CA1 glutamatergic synaptic transmission
Authors: Sun Jianli , Kapur Jaideep 
Published: June 2012

Key points
M‐type potassium channels play a key role in modulating neuronal excitability. However, the effects of M‐channel activation on synaptic transmission are poorly understood.
This study found that an M1 receptor agonist and M‐channel blockers increased action potential‐independent glutamate release at Schaffer collateral–CA1 pyramidal neuron synapses in acute hippocampus slices.
This enhancement was dependent on Ca2+ influx from extracellular space but not intracellular calcium stores.
Inhibition of M‐channels results in the depolarization of CA3 pyramidal neurons and activated presynaptic voltage‐gated P/Q‐ and N‐type calcium channels, which in turn causes Ca2+ influx and increased glutamate release.
Thus, M1 muscarinic agonists modulate action potential‐independent glutamatergic synaptic transmission in the hippocampus by inhibition of presynaptic M‐channels.
Abstract  Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M‐type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M‐type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN‐A‐343, increased the frequency of mEPSCs, but did not alter their amplitude. The M‐channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M‐channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium‐free external medium. Blocking P/Q‐ and N‐type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M‐channels increases presynaptic calcium‐dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M‐channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN‐A‐343 and XE991; these effects were consistent with the closure of M‐channels. Muscarinic activation inhibits M‐channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage‐gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons.
Assessment of HIV-1 Patient Recruitability in the Republic of Guinea-Bissau Using African versus North American Hematology and Biochemistry Reference Intervals
Authors: Gómez Román Victor Raúl , Jensen Sanne Skov , Leo-Hansen Christian , Jensen Kristoffer Jarlov , Janitzek Christoph Mikkel , Rodrigues Candida Medina , Jespersen Sanne , Katzenstein Terese Lea , da Silva Té David , Fomsgaard Anders 
Published: June 2012

ABSTRACTHematology and biochemistry reference intervals have been derived from healthy, HIV-negative populations to guide clinical trials worldwide. However, it is less clear how such values may be applied to clinical trials involving HIV-infected individuals. We show that contradictory interpretations about patient recruitability are reached when applying African versus North American reference intervals to an HIV-1 cohort in Guinea-Bissau. These observations underscore the need to question non-African guidelines in the context of HIV intervention clinical trials in Africa.
Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR
34
/L98H Azole Resistance Mechanism
Authors: Camps Simone M. T. , Rijs Antonius J. M. M. , Klaassen Corné H. W. , Meis Jacques F. , O'Gorman Céline M. , Dyer Paul S. , Melchers Willem J. G. , Verweij Paul E. 
Published: June 2012

ABSTRACT

A rapid emergence of azole resistance has been observed in
Aspergillus fumigatus
in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR
34
/L98H mutations in
cyp51A
. This resistance mechanism is now also increasingly being found in other countries. Therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. Studies of 142 European isolates revealed that those with the TR
34
/L98H resistance mechanism showed less genetic variation than azole-susceptible isolates or those with a different genetic basis of resistance and were assigned to only four CSP (putative cell surface protein) types. Sexual crossing experiments demonstrated that TR
34
/L98H isolates could outcross with azole-susceptible isolates of different genetic backgrounds, suggesting that TR
34
/L98H isolates can undergo the sexual cycle in nature. Overall, our findings suggest a common ancestor of the TR
34
/L98H mechanism and subsequent migration of isolates harboring TR
34
/L98H across Europe.
Automated Detection of Toxigenic Clostridium difficile in Clinical Samples: Isothermal
tcdB
Amplification Coupled to Array-Based Detection
Authors: Hicke Brian , Pasko Chris , Groves Benjamin , Ager Edward , Corpuz Maylene , Frech Georges , Munns Denton , Smith Wendy , Warcup Ashley , Denys Gerald , Ledeboer Nathan A. , Lindsey Wes , Owen Charles , Rea Larry , Jenison Robert 
Published: June 2012

ABSTRACT

Clostridium difficile
can carry a genetically variable pathogenicity locus (PaLoc), which encodes clostridial toxins A and B. In hospitals and in the community at large, this organism is increasingly identified as a pathogen. To develop a diagnostic test that combines the strengths of immunoassays (cost) and DNA amplification assays (sensitivity/specificity), we targeted a genetically stable PaLoc region, amplifying
tcdB
sequences and detecting them by hybridization capture. The assay employs a hot-start isothermal method coupled to a multiplexed chip-based readout, creating a manual assay that detects toxigenic
C. difficile
with high sensitivity and specificity within 1 h. Assay automation on an electromechanical instrument produced an analytical sensitivity of 10 CFU (95% probability of detection) of
C. difficile
in fecal samples, along with discrimination against other enteric bacteria. To verify automated assay function, 130 patient samples were tested: 31/32 positive samples (97% sensitive; 95% confidence interval [CI], 82 to 99%) and 98/98 negative samples (100% specific; 95% CI, 95 to 100%) were scored correctly. Large-scale clinical studies are now planned to determine clinical sensitivity and specificity.
Efficient Quantification of HIV-1 in Heparin Plasma Spiked with Cultured HIV-1 by the Roche Cobas TaqMan and Abbott RealTime HIV-1 Tests
Authors: Jagodzinski Linda L. , Weston Holly R. , Liu Ying , O'Connell Robert J. , Peel Sheila A. 
Published: June 2012

ABSTRACT
The current automated real-time HIV-1 viral load assays, the Roche Cobas AmpliPrep/Cobas TaqMan test and the Abbott RealTime test, are FDA cleared for use with EDTA plasma. We show that both real-time reverse transcription-PCR (RT-PCR) tests reliably quantify HIV-1 RNA in heparin plasma specimens spiked with HIV-1 isolate MN.
Prosthetic Valve Endocarditis Caused by a Pasteurella dagmatis-Like Isolate Originating from a Patient's Cat
Authors: Strahm Carol , Goldenberger Daniel , Gutmann Marc , Kuhnert Peter , Graber Peter 
Published: June 2012

ABSTRACT

Pasteurella
species are part of the oral flora of cats and dogs. In humans, they are frequently found in infected animal bite wounds, but invasive infections are rare. This is the first report of prosthetic-valve endocarditis with a
Pasteurella dagmatis
-like species, which originated from the patient's cat.
Effect of Priming with H1N1 Influenza Viruses of Variable Antigenic Distances on Challenge with 2009 Pandemic H1N1 Virus
Authors: O'Donnell Christopher D. , Wright Amber , Vogel Leatrice N. , Wei Chih-Jen , Nabel Gary J. , Subbarao Kanta 
Published: June 2012

ABSTRACTCompared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.
Structural Variability of the Herpes Simplex Virus 1 Genome
In Vitro
and
In Vivo
Authors: Mahiet Charlotte , Ergani Ayla , Huot Nicolas , Alende Nicolas , Azough Ahmed , Salvaire Fabrice , Bensimon Aaron , Conseiller Emmanuel , Wain-Hobson Simon , Labetoulle Marc , Barradeau Sébastien 
Published: June 2012

ABSTRACT

Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial-oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation.
In vivo
, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the one
in vitro
was observed, along with a considerable proportion of noncanonical assortment.
Naturally Occurring Swine Influenza A Virus PB1-F2 Phenotypes That Contribute to Superinfection with Gram-Positive Respiratory Pathogens
Authors: Weeks-Gorospe Jenni N. , Hurtig Heather R. , Iverson Amy R. , Schuneman Margaret J. , Webby Richard J. , McCullers Jonathan A. , Huber Victor C. 
Published: June 2012

ABSTRACT

A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of
Streptococcus pneumoniae
superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens:
Streptococcus pneumoniae
,
Staphylococcus aureus
, and
Streptococcus pyogenes
. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with
Streptococcus pyogenes
superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens.
FOXO3 Regulates the CD8 T Cell Response to a Chronic Viral Infection
Authors: Sullivan Jeremy A. , Kim Eui Ho , Plisch Erin H. , Suresh M. 
Published: June 2012

ABSTRACT

Chronic infections with viruses such as hepatitis B virus, hepatitis C virus, and HIV constitute a major global public health problem. Studies of chronic viral infections in humans and mice show that persistent antigenic stimulation induces dysregulation of T cell responses; virus-specific T cells either undergo clonal deletion or lose their ability to display the full spectrum of effector functions, a condition termed functional exhaustion. The ability to generate and retain sufficient numbers of functionally competent T cells, therefore, becomes vitally important in controlling chronic viral infections. Our understanding of the mechanisms governing T cell homeostasis during chronic viral infections, however, is poor. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway controls cell fate decisions in many cell types by modulating the activity of downstream effectors, including the FOXO family of transcription factors. We have observed dynamic,
in vivo
alterations in the phosphorylation levels of three key proteins (Akt, FOXO1/FOXO3 [FOXO1/3], and mammalian target of rapamycin [mTOR]) involved in this signaling cascade and have identified the transcription factor FOXO3 as a negative regulator of the magnitude and effector function of CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. We report that ablation of FOXO3 in T cells reduced apoptosis, increased the abundance of polyfunctional virus-specific CD8 T cells, and improved viral control. Thus, FOXO3 is a promising candidate target for immunotherapies of chronic viral infection.
Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon by Binding to MAVS and Decreasing Mitochondrial Membrane Potential
Authors: Varga Zsuzsanna T. , Grant Alesha , Manicassamy Balaji , Palese Peter 
Published: June 2012

ABSTRACT
PB1-F2 is a small, 87- to 90-amino-acid-long protein encoded by the +1 alternate open reading frame of the PB1 gene of most influenza A virus strains. It has been shown to contribute to viral pathogenicity in a host- and strain-dependent manner, and we have previously discovered that a serine at position 66 (66S) in the PB1-F2 protein increases virulence of the 1918 and H5N1 pandemic viruses. Recently, we have shown that PB1-F2 inhibits the induction of type I interferon (IFN) at the level of the MAVS adaptor protein. However, the molecular mechanism for the IFN antagonist function of PB1-F2 has remained unclear. In the present study, we demonstrated that the C-terminal portion of the PB1-F2 protein binds to MAVS in a region that contains the transmembrane domain. Strikingly, PB1-F2 66S was observed to bind to MAVS more efficiently than PB1-F2 66N. We also tested the effect of PB1-F2 on the IFN antagonist functions of the polymerase proteins PB1, PB2, and PA and observed enhanced IFN inhibition by the PB1 and PB2 proteins in combination with PB1-F2 but not by the PA protein. Using a flow cytometry-based assay, we demonstrate that the PB1-F2 protein inhibits MAVS-mediated IFN synthesis by decreasing the mitochondrial membrane potential (MMP). Interestingly, PB1-F2 66S affected the MMP more efficiently than wild-type PB1-F2. In summary, the results of our study identify the molecular mechanism by which the influenza virus PB1-F2 N66S protein increases virulence.
Hepatitis C Virus Infection Alters P-Body Composition but Is Independent of P-Body Granules
Authors: Pérez-Vilaró Gemma , Scheller Nicoletta , Saludes Verónica , Díez Juana 
Published: June 2012

ABSTRACTProcessing bodies (P-bodies) are highly dynamic cytoplasmic granules conserved among eukaryotes. They are present under normal growth conditions and contain translationally repressed mRNAs together with proteins from the mRNA decay and microRNA (miRNA) machineries. We have previously shown that the core P-body components PatL1, LSm1, and DDX6 (Rck/p54) are required for hepatitis C virus (HCV) RNA replication; however, how HCV infection affects P-body granules and whether P-body granulesper seinfluence the HCV life cycle remain unresolved issues. Here we show that HCV infection alters P-body composition by specifically changing the localization pattern of P-body components that are required for HCV replication. This effect was not related to an altered expression level of these components and could be reversed by inhibiting HCV replication with a polymerase inhibitor. Similar observations were obtained with a subgenomic replicon that supports only HCV translation and replication, indicating that these early steps of the HCV life cycle trigger the P-body alterations. Finally, P-body disruption by Rap55 depletion did not affect viral titers or HCV protein levels, demonstrating that the localization of PatL1, LSm1, and DDX6 in P-bodies is not required for their function on HCV. Thus, the HCV-induced changes on P-bodies are mechanistically linked to the function of specific P-body components in HCV RNA translation and replication; however, the formation of P-body granules is not required for HCV infection.
Solution Structure, Conformational Dynamics, and CD4-Induced Activation in Full-Length, Glycosylated, Monomeric HIV gp120
Authors: Guttman Miklos , Kahn Maria , Garcia Natalie K. , Hu Shiu-Lok , Lee Kelly K. 
Published: June 2012

ABSTRACT
The gp120 subunit of the HIV Env glycoprotein is responsible for receptor interactions leading to viral entry and is a primary target for neutralizing antibodies. Most structural studies have focused on the heavily truncated, deglycosylated gp120 core, leaving fundamental aspects of the glycoprotein that are responsible for immune evasion and receptor-induced activation unresolved. Here we investigate full-length, glycosylated HIV gp120 in unliganded and CD4-bound forms by using small-angle X-ray scattering to visualize global structural reorganization and hydrogen/deuterium exchange to track changes in local conformational dynamics. The studies revealed unliganded full-length gp120 to be considerably more dynamic, particularly at the CD4 binding site, than suggested by previous studies of the subunit core alone. The large V1/V2 loops, previously unmapped, are positioned to mask the coreceptor binding site in an orientation that recapitulates that observed in the Env trimer. CD4 binding shifts V1/V2 to unmask the coreceptor binding site and triggers profound dynamic changes in gp120 spanning from the binding site to the gp41-interactive face of gp120. These findings provide further insights on the structural basis of Env antigenicity and immunogenicity and of allosteric effects upon receptor binding.
The use of dynamic landscape metapopulation models for forest management: a case study of the red-backed salamander
Authors: Gordon Ascelin , Wintle Brendan A. , Bekessy Sarah A. , Pearce Jennie L. , Venier Lisa A. , Wilson Joab N. 
Published: June 2012

Spatial models of population dynamics have been proposed as a useful method for predicting the impacts of environmental change on biodiversity. Here, we demonstrate advances in dynamic landscape metapopulation modelling and its use as a decision support tool for evaluating the impacts of forest management scenarios. This novel modelling framework incorporates both landscape and metapopulation model stochasticity and allows their relative contributions to model output variance to be characterized. It includes a detailed sensitivity analysis, allowing defensible uncertainty bounds and the prioritization of future data gathering to reduce model uncertainties. We demonstrate this framework by modelling the landscape-level impacts of eight forest management scenarios on the red-backed salamander ( Plethodon cinereus (Green, 1818)) in the boreal forest of Ontario, Canada, using the RAMAS Landscape package. The 100 year forest management scenarios ranged in intensity of timber harvesting and fire suppression. All scenarios including harvesting predicted decreases in salamander population size and the current style of forest management is predicted to produce a 9%–17% decrease in expected minimum population size compared with scenarios without harvesting. This method is amenable to incorporating many forms of environmental change and allows a meaningful treatment of uncertainty.