bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrograde Axon Transport of Herpes Simplex Virus and Pseudorabies Virus: a Live-Cell Comparative Analysis
Authors: Antinone Sarah Elizabeth , Smith Gregory Allan 
Published: November 2009

ABSTRACT
Upon entry, neuroinvasive herpesviruses traffic from axon terminals to the nuclei of neurons resident in peripheral ganglia, where the viral DNA is deposited. A detailed analysis of herpes simplex virus type 1 (HSV-1) transport dynamics in axons following entry is currently lacking. Here, time lapse fluorescence microscopy was used to compare the postentry viral transport of two neurotropic herpesviruses: HSV-1 and pseudorabies virus (PRV). HSV-1 capsid transport dynamics were indistinguishable from those of PRV and did not differ in neurons of human, mouse, or avian origin. Simultaneous tracking of capsids and tegument proteins demonstrated that the composition of actively transporting HSV-1 is remarkably similar to that of PRV. This quantitative assessment of HSV-1 axon transport following entry demonstrates that HSV-1 and PRV share a conserved mechanism for postentry retrograde transport in axons and provides the foundation for further studies of the retrograde transport process.
The pH of Activation of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity and Transmissibility in Ducks
Authors: Reed Mark L. , Bridges Olga A. , Seiler Patrick , Kim Jeong-Ki , Yen Hui-Ling , Salomon Rachelle , Govorkova Elena A. , Webster Robert G. , Russell Charles J. 
Published: November 2009

ABSTRACT

While the molecular mechanism of membrane fusion by the influenza virus hemagglutinin (HA) protein has been studied extensively
in vitro
, the role of acid-dependent HA protein activation in virus replication, pathogenesis, and transmission
in vivo
has not been characterized. To investigate the biological significance of the pH of activation of the HA protein, we compared the properties of four recombinant viruses with altered HA protein acid stability to those of wild-type influenza virus A/chicken/Vietnam/C58/04 (H5N1)
in vitro
and in mallards. Membrane fusion by wild-type virus was activated at pH 5.9. Wild-type virus had a calculated environmental persistence of 62 days and caused extensive morbidity, mortality, shedding, and transmission in mallards. An N114K mutation that increased the pH of HA activation by 0.5 unit resulted in decreased replication, genetic stability, and environmental stability. Changes of +0.4 and −0.5 unit in the pH of activation by Y23H and K58I mutations, respectively, reduced weight loss, mortality, shedding, and transmission in mallards. An H24Q mutation that decreased the pH of activation by 0.3 unit resulted in weight loss, mortality, clinical symptoms, and shedding similar to those of the wild type. However, the HA-H24
1
Q virus was shed more extensively into drinking water and persisted longer in the environment. The pH of activation of the H5 HA protein plays a key role in the propagation of H5N1 influenza viruses in ducks and may be a novel molecular factor in the ecology of influenza viruses. The data also demonstrate that H5N1 neuraminidase activity increases the pH of activation of the HA protein
in vitro
.
Discrimination of Mixed- versus Ice-Phase Clouds Using Dual-Polarization Radar with Application to Detection of Aircraft Icing Regions*
Authors: Plummer David M. , Göke Sabine , Rauber Robert M. , Di Girolamo Larry 
Published: November 2009

AbstractDual-polarization radar measurements and in situ measurements of supercooled liquid water and ice particles within orographic cloud systems are used to develop probabilistic criteria for identifying mixed-phase versus ice-phase regions of sub-0°C clouds. The motivation for this study is the development of quantitative criteria for identification of potential aircraft icing conditions in clouds using polarization radar. The measurements were obtained during the Mesoscale Alpine Programme (MAP) with the National Center for Atmospheric Research S-band dual-polarization Doppler radar (S-Pol) and Electra aircraft. The comparison of the radar and aircraft measurements required the development of an automated algorithm to match radar and aircraft observations in time and space. This algorithm is described, and evaluations are presented to verify its accuracy. Three polarization radar parameters, the radar reflectivity factor at horizontal polarization (ZH), the differential reflectivity (ZDR), and the specific differential phase (KDP), are first separately shown to be statistically distinguishable between conditions in mixed- and ice-phase clouds, even when an estimate of measurement uncertainty is included. Probability distributions for discrimination of mixed-phase versus ice-phase clouds are then developed using the matched radar and aircraft measurements. The probability distributions correspond well to a basic physical understanding of ice particle growth by riming and vapor deposition, both of which may occur in mixed-phase conditions. To the extent that the probability distributions derived for the MAP orographic clouds can be applied to other cloud systems, they provide a simple tool for warning aircraft of the likelihood that supercooled water may be encountered in regions of clouds.
Evaluating the Impact of the Number of Satellite Altimeters Used in an Assimilative Ocean Prediction System
Authors: Helber Robert W. , Shriver Jay F. , Barron Charlie N. , Smedstad Ole Martin 
Published: November 2009

Abstract
The impact of the number of satellite altimeters providing sea surface height anomaly (SSHA) information for a data assimilation system is evaluated using two comparison frameworks and two statistical methodologies. The Naval Research Laboratory (NRL) Layered Ocean Model (NLOM) dynamically interpolates satellite SSHA track data measured from space to produce high-resolution (eddy resolving) fields. The Modular Ocean Data Assimilation System (MODAS) uses the NLOM SSHA to produce synthetic three-dimensional fields of temperature and salinity over the global ocean. A series of case studies is defined where NLOM assimilates different combinations of data streams from zero to three altimeters. The resulting NLOM SSHA fields and the MODAS synthetic profiles are evaluated relative to independently observed ocean temperature and salinity profiles for the years 2001–03. The NLOM SSHA values are compared with the difference of the observed dynamic height from the climatological dynamic height. The synthetics are compared with observations using a measure of thermocline depth. Comparisons are done point for point and for 1° radius regions that are linearly fit over 2-month periods. To evaluate the impact of data outliers, statistical evaluations are done with traditional Gaussian statistics and also with robust nonparametric statistics. Significant error reduction is obtained, particularly in high SSHA variability regions, by including at least one altimeter. Given the limitation of these methods, the overall differences between one and three altimeters are significant only in bias. Data outliers increase Gaussian statistical error and error uncertainty compared to the same computations using nonparametric statistical methods.
A Vector Geometry–Based Eddy Detection Algorithm and Its Application to a High-Resolution Numerical Model Product and High-Frequency Radar Surface Velocities in the Southern California Bight
Authors: Nencioli Francesco , Dong Changming , Dickey Tommy , Washburn Libe , McWilliams James C. 
Published: November 2009

Abstract
Automated eddy detection methods are fundamental tools to analyze eddy activity from the large datasets derived from satellite measurements and numerical model simulations. Existing methods are either based on the distribution of physical parameters usually computed from velocity derivatives or on the geometry of velocity streamlines around minima or maxima of sea level anomaly. A new algorithm was developed based exclusively on the geometry of the velocity vectors. Four constraints characterizing the spatial distribution of the velocity vectors around eddy centers were derived from the general features associated with velocity fields in the presence of eddies. The grid points in the domain for which these four constraints are satisfied are detected as eddy centers. Eddy sizes are computed from closed contours of the streamfunction field, and eddy tracks are retrieved by comparing the distribution of eddy centers at successive time steps. The results were validated against manually derived eddy fields. Two parameters in the algorithm can be modified by the users to optimize its performance. The algorithm is applied to both a high-resolution model product and high-frequency radar surface velocity fields in the Southern California Bight.
Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6
Authors: Loges Sonja , Schmidt Thomas , Tjwa Marc , van Geyte Katie , Lievens Dirk , Lutgens Esther , Vanhoutte Davy , Borgel Delphine , Plaisance Stephane , Hoylaerts Marc , Luttun Aernout , Dewerchin Mieke , Jonckx Bart , Carmeliet Peter 
Published: November 2009

AbstractThe transforming and tumor growth–promoting properties of Axl, a member of the Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases (TAMRs), are well recognized. In contrast, little is known about the role of the TAMR ligand growth arrest–specific gene 6 (Gas6) in tumor biology. By using Gas6-deficient (Gas6−/−) mice, we show that bone marrow–derived Gas6 promotes growth and metastasis in different experimental cancer models, including one resistant to vascular endothelial growth factor inhibitors. Mechanistic studies reveal that circulating leukocytes produce minimal Gas6. However, once infiltrated in the tumor, leukocytes up-regulate Gas6, which is mitogenic for tumor cells. Consistent herewith, impaired tumor growth in Gas6−/− mice is rescued by transplantation of wild-type bone marrow and, conversely, mimicked by transplantation of Gas6−/− bone marrow into wild-type hosts. These findings highlight a novel role for Gas6 in a positive amplification loop, whereby tumors promote their growth by educating infiltrating leukocytes to up-regulate the production of the mitogen Gas6. Hence, inhibition of Gas6 might offer novel opportunities for the treatment of cancer.
Immunization with host-type CD8α+ dendritic cells reduces experimental acute GVHD in an IL-10–dependent manner
Authors: Toubai Tomomi , Malter Chelsea , Tawara Isao , Liu Chen , Nieves Evelyn , Lowler Kathleen P. , Sun Yaping , Reddy Pavan 
Published: November 2009

AbstractLittle is known about the role of active immunization in suppressing undesirable immune responses. Because CD8α+ dendritic cells (DCs) suppress certain immune responses, we tested the hypothesis that immunization of donors with host-derived CD8α+ DCs will reduce host-specific donor T-cell responses. BALB/c T cells from the animals that were immunized with B6 CD8α+ DCs demonstrated, in vitro and in vivo, significantly reduced proliferation and secretion of inflammatory cytokines but showed enhanced secretion of interleukin-10 (IL-10). The responses against third-party and model antigens were preserved demonstrating antigen specificity. The in vivo relevance was further demonstrated by the reduction on graft-versus-host disease (GVHD) in both a major histocompatibility complex–mismatched clinically relevant BALB/c → B6 model and major histocompatibility complex–matched, minor-mismatched C3H.SW → B6 model of GVHD. Immunization of the donors that were deficient in IL-10 (IL-10−/−) or with CD8α+ DCs from B6 class II (class II−/−) failed to reduce T-cell responses, demonstrating (1) a critical role for secretion of IL-10 by donor T cells and (2) a direct contact between the T cells and the CD8α+ DCs. Together, these data may represent a novel strategy for reducing GVHD and suggest a broad counterintuitive role for vaccination strategies in mitigating undesirable immune responses in an antigen-specific manner.
The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia
Authors: Lubenow Norbert , Hinz Peter , Thomaschewski Simone , Lietz Theresia , Vogler Michael , Ladwig Andrea , Jünger Michael , Nauck Matthias , Schellong Sebastian , Wander Kathrin , Engel Georg , Ekkernkamp Axel , Greinacher Andreas 
Published: November 2009

Abstract
Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently.
Nonlinear preprocessing method for detecting peaks from gas chromatograms
Authors: Shim Byonghyo , Min Hyeyoung , Yoon Sungroh 
Published: November 2009

Abstract

Background
The problem of locating valid peaks from data corrupted by noise frequently arises while analyzing experimental data. In various biological and chemical data analysis tasks, peak detection thus constitutes a critical preprocessing step that greatly affects downstream analysis and eventual quality of experiments. Many existing techniques require the users to adjust parameters by trial and error, which is error-prone, time-consuming and often leads to incorrect analysis results. Worse, conventional approaches tend to report an excessive number of false alarms by finding fictitious peaks generated by mere noise.

Results
We have designed a novel peak detection method that can significantly reduce parameter sensitivity, yet providing excellent peak detection performance and negligible false alarm rates from gas chromatographic data. The key feature of our new algorithm is the successive use of peak enhancement algorithms that are deliberately designed for a gradual improvement of peak detection quality. We tested our approach with real gas chromatograms as well as intentionally contaminated spectra that contain Gaussian or speckle-type noise.

Conclusion
Our results demonstrate that the proposed method can achieve near perfect peak detection performance while maintaining very small false alarm probabilities in case of gas chromatograms. Given the fact that biological signals appear in the form of peaks in various experimental data and that the propose method can easily be extended to such data, our approach will be a useful and robust tool that can help researchers highlight valid signals in their noisy measurements.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells
Authors: Calligaris Raffaella , Bellarosa Cristina , Foti Rossana , Roncaglia Paola , Giraudi Pablo , Krmac Helena , Tiribelli Claudio , Gustincich Stefano 
Published: November 2009

AbstractBackgroundThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown.ResultsTranscriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER) stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis ofXBP1splicing and DDIT3/CHOP subcellular localization is presented.ConclusionThese results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro.
The choroid plexus response to a repeated peripheral inflammatory stimulus
Authors: Marques Fernanda , Sousa João C , Coppola Giovanni , Geschwind Daniel H , Sousa Nuno , Palha Joana A , Correia-Neves Margarida 
Published: November 2009

AbstractBackgroundChronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid.ResultsIn the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection.ConclusionThese observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated.
A novel study of Copy Number Variations in Hirschsprung disease using the Multiple Ligation-dependent Probe Amplification (MLPA) technique
Authors: Núñez-Torres Rocío , Fernández Raquel M , López-Alonso Manuel , Antiñolo Guillermo , Borrego Salud 
Published: November 2009

Abstract

Background
Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis.

Methods
In this study we have aimed to analyze the presence of CNVs in some HSCR genes (RET, EDN3, GDNF and ZFHX1B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach.

Results
Two alterations in the MLPA profiles of RET and EDN3 were detected, but a detailed inspection showed that the decrease in the corresponding dosages were due to point mutations affecting the hybridization probes regions.

Conclusion
Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes.
Quantifying the treatment efficacy of reverse transcriptase inhibitors: new analyses of clinical data based on within-host modeling
Authors: Breban Romulus , Napravnik Sonia , Kahn James , Blower Sally 
Published: November 2009

AbstractBackgroundCurrent measures of the clinical efficacy of antiretroviral therapy (ART) in the treatment of HIV include the change in HIV RNA in the plasma and the gain in CD4 cells.MethodsWe propose new measures for evaluating the efficacy of treatment that is based upon combinations of non-nucleoside and nucleoside reverse transcriptase inhibitors. Our efficacy measures are: theCD4 gain per virion eliminated, thepotential of CD4 count restoration and the viral reproduction number (R0). These efficacy measures are based upon a theoretical understanding of the impact of treatment on both viral dynamics and the immune reconstitution. Patient data were obtained from longitudinal HIV clinical cohorts.ResultsWe found that theCD4 cell gain per virion eliminatedranged from 10-2to 600 CD4 cells/virion, thepotential of CD4 count restorationranged from 60 to 1520 CD4 cells/μl, and the basic reproduction number was reduced from an average of 5.1 before therapy to an average of 1.2 after one year of therapy. There was substantial heterogeneity in these efficacy measures among patients with detectable viral replication. We found that many patients who achieved viral suppression did not have high CD4 cell recovery profiles. Our efficacy measures also enabled us to identify a subgroup of patients who were not virally suppressed but had the potential to reach a high CD4 count and/or achieve viral suppression if they had been switched to a more potent regimen.ConclusionWe show that our new efficacy measures are useful for analyzing the long-term treatment efficacy of combination reverse transcriptase inhibitors and argue that achieving a lowR0does not imply achieving viral suppression.
The expression of Gli3, regulated by HOXD13, may play a role in idiopathic congenital talipes equinovarus
Authors: Cao DongHua , Jin ChunLian , Ren MeiHong , Lin ChangKun , Zhang Xuan , Zhao Ning 
Published: November 2009

Abstract

Background
Idiopathic congenital talipes equinovarus (ICTEV) is a congenital limb deformity. Based on extended transmission disequilibrium testing, Gli-Kruppel family member 3 (Gli3) has been identified as a candidate gene for ICTEV. Here, we verify the role of Gli3 in ICTEV development.

Methods
Using the rat ICTEV model, we analyzed the differences in Gli3 expression levels between model rats and normal control rats. We used luciferase reporter gene assays and ChIP/EMSA assays to analyze the regulatory elements of Gli3.

Results

Gli3 showed higher expression levels in ICTEV model rats compared to controls (P < 0.05). We identified repressor and activator regions in the rat Gli3 promoter. The Gli3 promoter also contains two putative Hoxd13 binding sites. Using EMSA, the Hoxd13 binding site 2 was found to directly interact with Hoxd13 in vitro. ChIP assays of the Hoxd13-Gli3 promoter complex from a developing limb confirmed that endogenous Hoxd13 interacts with this region in vivo.

Conclusion
Our findings suggest that HoxD13 directly interacts with the promoter of Gli3. The increase of Gli3 expression in ICTEV model animal might result from the low expression of HoxD13.