bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxsackievirus B4 Uses Autophagy for Replication after Calpain Activation in Rat Primary Neurons
Authors: Yoon Seung Yong , Ha Young Eun , Choi Jung Eun , Ahn Jeonghyun , Lee Heuiran , Kweon Hee-Seok , Lee Jee-Young , Kim Dong Hou 
Published: September 2008

ABSTRACT
Coxsackievirus is the most important cause of meningitis and encephalitis in infants; an infection is sometimes fatal or may lead to neurodevelopmental defects. Here, we show that coxsackievirus B4 (CVB4) induces an autophagy pathway for replication in rat primary neurons. Notably, calpain inhibitors reduce autophagosome formation. Conversely, the inhibition of the autophagy pathway with 3-methyladenine inhibits calpain activation. This work reveals, for the first time, that calpain is essential for the autophagy pathway and viral replication in CVB4-infected neurons.
Induction of Cellular Stress Overcomes the Requirement of Herpes Simplex Virus Type 1 for Immediate-Early Protein ICP0 and Reactivates Expression from Quiescent Viral Genomes
Authors: Preston Chris M. , Nicholl Mary Jane 
Published: September 2008

ABSTRACT
Herpes simplex virus type 1 (HSV-1) mutants impaired in the activities of the structural protein VP16 and the immediate-early (IE) proteins ICP0 and ICP4 establish a quiescent infection in human fibroblasts, with most cells retaining an inactive, repressed viral genome for sustained periods in culture. To date, the quiescent state has been considered stable, since it has been reversed only by provision of herpesviral proteins, such as ICP0, not by alteration of the cell physiological state. We report that the interaction of HSV-1 with human fibroblasts can be altered significantly by transient treatment of cultures with sodium arsenite, an inducer of heat shock and oxidative stress, or gramicidin D, a toxin that selectively permeabilizes cell membranes, prior to infection. These regimens stimulated gene expression from IE-deficient HSV-1 mutants in a promoter sequence-independent manner and also overcame the replication defect of ICP0-null mutants. Reactivation of gene expression from quiescent HSV-1 genomes and the resumption of virus replication were observed following addition of arsenite or gramicidin D to cultures. Both agents induced reorganization of nuclear domain 10 structures, the sites of quiescent genomes, but appeared to do so through different mechanisms. The results demonstrate that the physiological state of the cell is important in determining the outcome of infection with IE-deficient HSV-1 and show novel methods for reactivating quiescent HSV-1 in fibroblasts with a high efficiency.
Baseline Resistance of Primary Human Immunodeficiency Virus Type 1 Strains to the CXCR4 Inhibitor AMD3100
Authors: Harrison Jessamina E. , Lynch Jonathan B. , Sierra Luz-Jeannette , Blackburn Leslie A. , Ray Neelanjana , Collman Ronald G. , Doms Robert W. 
Published: September 2008

ABSTRACT
We screened a panel of R5X4 and X4 human immunodeficiency virus type 1 (HIV-1) strains for their sensitivities to AMD3100, a small-molecule CXCR4 antagonist that blocks HIV-1 infection via this coreceptor. While no longer under clinical development, AMD3100 is a useful tool with which to probe interactions between the viral envelope (Env) protein and CXCR4 and to identify pathways by which HIV-1 may become resistant to this class of antiviral agents. While infection by most virus strains was completely blocked by AMD3100, we identified several R5X4 and X4 isolates that exhibited plateau effects: as the AMD3100 concentration was increased, virus infection and membrane fusion diminished to variable degrees. Once saturating concentrations of AMD3100 were achieved, further inhibition was not observed, indicating a noncompetitive mode of viral resistance to the drug. The magnitude of the plateau varied depending on the virus isolate, as well as the cell type used, with considerable variation observed when primary human T cells from different human donors were used. Structure-function studies indicated that the V1/V2 region of the R5X4 HIV-1 isolate DH12 was necessary for AMD3100 resistance and could confer this property on two heterologous Env proteins. We conclude that some R5X4 and X4 HIV-1 isolates can utilize the AMD3100-bound conformation of CXCR4, with the efficiency being influenced by both viral and host factors. Baseline resistance to this CXCR4 antagonist could influence the clinical use of such compounds.
Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding
Authors: Wilda Maximiliano , Lopez Nora , Casabona Juan Cruz , Franze-Fernandez Maria T. 
Published: September 2008

ABSTRACT

Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV-like RNAs and that Z is a powerful inhibitor of these processes (Lopez et al., J. Virol.
65:
12241-12251, 2001). More recently, we provided the first evidence of an interaction between Z and L and showed that Z's inhibitory activity was dependent on its ability to bind to L (Jácamo et al., J. Virol.
77:
10383-10393, 2003). In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z.
Biochemical and Biophysical Characterization of a Chimeric TRIM21-TRIM5α Protein
Authors: Kar Alak Kanti , Diaz-Griffero Felipe , Li Yuan , Li Xing , Sodroski Joseph 
Published: September 2008

ABSTRACT

The tripartite motif (TRIM) protein, TRIM5α, is an endogenous factor in primates that recognizes the capsids of certain retroviruses after virus entry into the host cell. TRIM5α promotes premature uncoating of the capsid, thus blocking virus infection. Low levels of expression and tendencies to aggregate have hindered the biochemical, biophysical, and structural characterization of TRIM proteins. Here, a chimeric TRIM5α protein (TRIM5
Rh
-21R) with a RING domain derived from TRIM21 was expressed in baculovirus-infected insect cells and purified. Although a fraction of the TRIM5
Rh
-21R protein formed large aggregates, soluble fractions of the protein formed oligomers (mainly dimers), exhibited a protease-resistant core, and contained a high percentage of helical secondary structure. Cross-linking followed by negative staining and electron microscopy suggested a globular structure. The purified TRIM5
Rh
-21R protein displayed E3-ligase activity in vitro and also self-ubiquitylated in the presence of ubiquitin-activating and -conjugating enzymes. The purified TRIM5
Rh
-21R protein specifically associated with human immunodeficiency virus type 1 capsid-like complexes; a deletion within the V1 variable region of the B30.2(SPRY) domain decreased capsid binding. Thus, the TRIM5
Rh
-21R restriction factor can directly recognize retroviral capsid-like complexes in the absence of other mammalian proteins.
Identification and Characterization of PWWP Domain Residues Critical for LEDGF/p75 Chromatin Binding and Human Immunodeficiency Virus Type 1 Infectivity
Authors: Shun Ming-Chieh , Botbol Yaïr , Li Xiang , Di Nunzio Francesca , Daigle Janet E. , Yan Nan , Lieberman Judy , Lavigne Marc , Engelman Alan 
Published: September 2008

ABSTRACT
Lens epithelium-derived growth factor (LEDGF)/p75 functions as a bimodal tether during lentiviral DNA integration: its C-terminal integrase-binding domain interacts with the viral preintegration complex, whereas the N-terminal PWWP domain can bind to cellular chromatin. The molecular basis for the integrase-LEDGF/p75 interaction is understood, while the mechanism of chromatin binding is unknown. The PWWP domain is homologous to other protein interaction modules that together comprise the Tudor clan. Based on primary amino acid sequence and three-dimensional structural similarities, 24 residues of the LEDGF/p75 PWWP domain were mutagenized to garner essential details of its function during human immunodeficiency virus type 1 (HIV-1) infection. Mutating either Trp-21 or Ala-51, which line the inner wall of a hydrophobic cavity that is common to Tudor clan members, disrupts chromatin binding and virus infectivity. Consistent with a role for chromatin-associated LEDGF/p75 in stimulating integrase activity during infection, recombinant W21A protein is preferentially defective for enhancing integration into chromatinized target DNA in vitro. The A51P mutation corresponds to the S270P change in DNA methyltransferase 3B that causes human immunodeficiency, centromeric instability, and facial anomaly syndrome, revealing a critical role for this amino acid position in the chromatin binding functions of varied PWWP domains. Our results furthermore highlight the requirement for a conserved Glu in the hydrophobic core that mediates interactions between other Tudor clan members and their substrates. This initial systematic mutagenesis of a PWWP domain identifies amino acid residues critical for chromatin binding function and the consequences of their changes on HIV-1 integration and infection.
Estimating the Impact of Vaccination on Acute Simian-Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections
Authors: Petravic Janka , Ribeiro Ruy M. , Casimiro Danilo R. , Mattapallil Joseph J. , Roederer Mario , Shiver John W. , Davenport Miles P. 
Published: September 2008

ABSTRACT
The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, for the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in SHIV and SIV infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3- and 2-fold, respectively. This method allows the comparison of vaccination efficacies among different viral strains and animal models in vivo.
Assessing Meteorological Variable and Process Relationships to Modeled PM2.5 Ammonium Nitrate and Ammonium Sulfate in the Central United States
Authors: Baker Kirk , Scheff Peter 
Published: September 2008

Abstract
Many counties are required to submit an emissions control plan to the U.S. Environmental Protection Agency to reduce concentrations of particulate matter of less than 2.5 μm in diameter (PM2.5), which are dominated by ammonium sulfate and ammonium nitrate in the central United States. These control scenarios are simulated with photochemical models, which use emissions and meteorological variables to simulate PM2.5 formation, transport, and deposition. A monitor study was established in the central United States to measure simultaneously the PM2.5 sulfate ion, nitrate ion, ammonium ion, and chemical precursor species sulfur dioxide, nitric acid, and ammonia during 2004. These data, combined with nearby meteorological observations, provide an opportunity to assess whether meteorological variables or deposition processes may introduce systematic biases in PM2.5 ammonium sulfate and ammonium nitrate predictions. Skill in estimating total wet deposition is assessed by comparing model output with National Atmospheric Deposition Program monitors in the region. Meteorological variables that are important for mass transport (wind vector) and thermodynamic chemistry (temperature and relative humidity) compare well to observations. A model sensitivity, in which the temperatures in the inorganic chemistry module are adjusted to compensate for an underprediction bias, shows a minimal model response in predicted PM2.5 ammonium nitrate. The dry deposition of sulfur dioxide seems to have a systematic impact on ambient estimates of sulfur dioxide in the photochemical model. An attempt to correlate bias and error in meteorological variables to bias and error in PM2.5 species showed the most relationship between relative humidity and temperature and ammonium nitraite. Wet deposition of total sulfate, nitrate, and ammonium tend to be underpredicted in the winter months.
A Scalable Datalogging System with Serial Interfaces and Integrated GPS Time Stamping
Authors: Behn Mario , Hohreiter Vincent , Muschinski Andreas 
Published: September 2008

AbstractA scalable datalogging system for micrometeorological, fast-response, in situ, and remote sensing applications is presented. The system is based on a standard x86 MINI-ITX computer and the open-source operating system Linux. Real-time access for debugging and remote system control is implemented via a network interface. A 160-GB, 2.5-in. hard disk drive provides extended local storage. The recorded data can alternately be stored at a remote location using the Network File System (NFS) included in Linux. Accurate time stamping of collected data points is implemented using the open-source software Network Time Protocol (NTP) and a global positioning system (GPS) receiver. The operational capability of the system is demonstrated over a period of several weeks with data from seven ultrasonic anemometer–thermometers and a barometer.
A Technique for the Automatic Detection of Insect Clutter in Cloud Radar Returns
Authors: Luke Edward P. , Kollias Pavlos , Johnson Karen L. , Clothiaux Eugene E. 
Published: September 2008

Abstract
The U.S. Department of Energy Atmospheric Radiation Measurement (ARM) Program operates 35-GHz millimeter-wavelength cloud radars (MMCRs) in several climatologically distinct regions. The MMCRs, which are centerpiece instruments for the observation of clouds and precipitation, provide continuous, vertically resolved information on all hydrometeors above the ARM Climate Research Facilities (ACRF). However, their ability to observe clouds in the lowest 2–3 km of the atmosphere is often obscured by the presence of strong echoes from insects, especially during the warm months at the continental midlatitude Southern Great Plains (SGP) ACRF. Here, a new automated technique for the detection and elimination of insect-contaminated echoes from the MMCR observations is presented. The technique is based on recorded MMCR Doppler spectra, a feature extractor that conditions insect spectral signatures, and the use of a neural network algorithm for the generation of an insect (clutter) mask. The technique exhibits significant skill in the identification of insect radar returns (more than 92% of insect-induced returns are identified) when the sole input to the classifier is the MMCR Doppler spectrum. The addition of circular polarization observations by the MMCR and ceilometer cloud-base measurements further improve the performance of the technique and form an even more reliable method for the removal of insect radar echoes at the ARM site. Recently, a 94-GHz Doppler polarimetric radar was installed next to the MMCR at the ACRF SGP site. Observations by both radars are used to evaluate the potential of the 94-GHz radar as being insect free and to show that dual wavelength radar reflectivity measurements can be used to identify insect radar returns.
Loop Current Response to Hurricanes Isidore and Lili
Authors: Shay Lynn K. , Uhlhorn Eric W. 
Published: September 2008

Abstract
Recent hurricane activity over the Gulf of Mexico basin has underscored the importance of the Loop Current (LC) and its deep, warm thermal structure on hurricane intensity. During Hurricanes Isidore and Lili in 2002, research flights were conducted from both National Oceanic and Atmospheric Administration (NOAA) WP-3D aircraft to observe pre-, in- and poststorm ocean conditions using airborne expendable ocean profilers to measure temperature, salinity, and current structure. Atmospheric thermodynamic and wind profiles and remotely sensed surface winds were concurrently acquired as each storm moved over the LC.
Observed upper-ocean cooling was about 1°C as Isidore moved across the Yucatan Straits at a speed of 4 m s−1. Given prestorm ocean heat content (OHC) levels exceeding 100 kJ cm−2 in the LC (current velocities &gt;1 m s−1), significant cooling and deepening of the ocean mixed layer (OML) did not occur in the straits. Estimated surface enthalpy flux at Isidore’s eyewall was 1.8 kW m−2, where the maximum observed wind was 49 m s−1. Spatially integrating these surface enthalpy fluxes suggested a maximum surface heat loss of 9.5 kJ cm−2 at the eyewall. Over the Yucatan Shelf, observed ocean cooling of 4.5°C was caused by upwelling processes induced by wind stress and an offshore wind-driven transport. During Hurricane Lili, ocean cooling in the LC was ∼1°C but more than 2°C in the Gulf Common Water, where the maximum estimated surface enthalpy flux was 1.4 kW m−2, associated with peak surface winds of 51 m s−1. Because of Lili’s asymmetric structure and rapid translational speed of 7 m s−1, the maximum surface heat loss resulting from the surface enthalpy flux was less than 5 kJ cm−2.
In both hurricanes, the weak ocean thermal response in the LC was primarily due to the lack of energetic near-inertial current shears that develop across the thin OML observed in quiescent regimes. Bulk Richardson numbers remained well above criticality because of the strength of the upper-ocean horizontal pressure gradient that forces northward current and thermal advection of warm water distributed over deep layers. As these oceanic regimes are resistive to shear-induced mixing, hurricanes experience a more sustained surface enthalpy flux compared to storms moving over shallow quiescent mixed layers. Because ocean cooling levels induced by hurricane force winds depend on the underlying oceanic regimes, features must be accurately initialized in coupled forecast models.
An Object-Oriented Verification of Three NWP Model Formulations via Cluster Analysis: An Objective and a Subjective Analysis
Authors: Marzban Caren , Sandgathe Scott , Lyons Hilary 
Published: September 2008

Abstract
Recently, an object-oriented verification scheme was developed for assessing errors in forecasts of spatial fields. The main goal of the scheme was to allow the automatic and objective evaluation of a large number of forecasts. However, processing speed was an obstacle. Here, it is shown that the methodology can be revised to increase efficiency, allowing for the evaluation of 32 days of reflectivity forecasts from three different mesoscale numerical weather prediction model formulations. It is demonstrated that the methodology can address not only spatial errors, but also intensity and timing errors. The results of the verification are compared with those performed by a human expert.
For the case when the analysis involves only spatial information (and not intensity), although there exist variations from day to day, it is found that the three model formulations perform comparably, over the 32 days examined and across a wide range of spatial scales. However, the higher-resolution model formulation appears to have a slight edge over the other two; the statistical significance of that conclusion is weak but nontrivial. When intensity is included in the analysis, it is found that these conclusions are generally unaffected. As for timing errors, although for specific dates a model may have different timing errors on different spatial scales, over the 32-day period the three models are mostly “on time.” Moreover, although the method is nonsubjective, its results are shown to be consistent with an expert’s analysis of the 32 forecasts. This conclusion is tentative because of the focused nature of the data, spanning only one season in one year. But the proposed methodology now allows for the verification of many more forecasts.
Pain assessment tools in palliative care: an urgent need for consensus
Authors: Hjermstad MJ , Gibbins J , Haugen DF , Caraceni A , Loge JH , Kaasa S ,   On behalf of the EPCRC, European Palliative Care Research Collaborative
Published: September 2008

At present, there is no universally accepted cancer pain assessment tool for use in palliative care (PC). The European Palliative Care Research Collaborative (EPCRC), therefore, aims to develop an international consensus-based computerised pain assessment tool. As part of this process, we have performed (1) a literature review on pain assessment tools for use in the PC and (2) an international expert survey to gain information on the relevant dimensions for pain assessment in PC. 230 publications were identified, only six met the inclusion criteria. Three further articles were identified through manual searching, totalling 11 different pain assessment tools. Nine tools were multidimensional. Pain intensity was assessed in seven, using various numerical/verbal rating scales (NRS/VRS); five tools focused on pain management. Three publications did not identify the rationale for the need to develop a new tool, and the selection procedure for items/dimensions was not described in six tools. Patient and/or professional expert groups were involved in the development of five tools and only two tools were extensively validated or cross-culturally tested. Thirty-two experts (71%) completed the expert survey and identified ‘intensity’, ‘temporal pattern’, ‘relief/exacerbation’, ‘pain quality’ and ‘location’ as the five most relevant dimensions. Most preferred assessment of ‘pain intensity’ was by NRS rather than VRS. Time windows extending 24 h were regarded as less relevant. Development of PC pain assessment tools seems to be a continuous process, which does not adhere to systematic guidelines, thus does not contribute to a universally accepted tool. No tool contained all relevant dimensions as defined by the experts. Many tools focused on particular dimensions, suggesting that specific research interests may drive the tool development process. Extensive literature reviews, expert and patient input and clinical studies are a needed approach in the development of a new consensus-based pain assessment tool.