bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of Intracellular Zinc Inhibits the Ubiquitin Ligase Activity of Viral Regulatory Protein ICP0 and Restricts Herpes Simplex Virus 1 Replication in Cell Culture
Authors: Grant Kyle , Grant Louise , Tong Lily , Boutell Chris 
Published: January 2012

ABSTRACT

The viral ubiquitin ligase ICP0 stimulates the onset of HSV-1 lytic infection and productive reactivation of viral genomes from latency. In order to mediate these processes, it requires its C3HC4 RING finger domain, a tertiary structural fold that is coordinated by the binding of two zinc (Zn
2+
) atoms. Here we formally demonstrate that Zn
2+
binding and intracellular Zn
2+
levels are critical for ICP0's biochemical activity and that depletion of intracellular Zn
2+
severely attenuates HSV-1 replication.
Identification and Characterization of Equine Herpesvirus Type 1 pUL56 and Its Role in Virus-Induced Downregulation of Major Histocompatibility Complex Class I
Authors: Ma Guanggang , Feineis Silke , Osterrieder Nikolaus , Van de Walle Gerlinde R. 
Published: January 2012

ABSTRACT

Major histocompatibility complex class I (MHC-I) molecules play an important role in host immunity to infection by presenting antigenic peptides to cytotoxic T lymphocytes (CTLs), which recognize and destroy virus-infected cells. Members of the
Herpesviridae
have developed multiple mechanisms to avoid CTL recognition by virtue of downregulation of MHC-I on the cell surface. We report here on an immunomodulatory protein involved in this process, pUL56, which is encoded by
ORF1
of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus. We show that EHV-1 pUL56 is a phosphorylated early protein which is expressed as different forms and predominantly localizes to Golgi membranes. In addition, the transmembrane (TM) domain of the type II membrane protein was shown to be indispensable for correct subcellular localization and a proper function. pUL56 by itself is not functional with respect to interference with MHC-I and likely needs another unidentified viral protein(s) to perform this action. Surprisingly, pUL49.5, an inhibitor of the transporter associated with antigen processing (TAP) and encoded by EHV-1 and related viruses, appeared not to be required for pUL56-induced early MHC-I downmodulation in infected cells. In conclusion, our data identify a new immunomodulatory protein, pUL56, involved in MHC-I downregulation which is unable to perform its function outside the context of viral infection.
Inhibition of Human Papillomavirus DNA Replication by an E1-Derived p80/UAF1-Binding Peptide
Authors: Lehoux Michaël , Fradet-Turcotte Amélie , Lussier-Price Mathieu , Omichinski James G. , Archambault Jacques 
Published: January 2012

ABSTRACT

The papillomavirus E1 helicase is recruited by E2 to the viral origin, where it assembles into a double hexamer that orchestrates replication of the viral genome. We previously identified the cellular WD40 repeat-containing protein p80/UAF1 as a novel interaction partner of E1 from anogenital human papillomavirus (HPV) types. p80 was found to interact with the first 40 residues of HPV type 31 (HPV31) E1, and amino acid substitutions within this domain abrogated the maintenance of the viral episome in keratinocytes. In this study, we report that these p80-binding substitutions reduce by 70% the ability of E1 to support transient viral DNA replication without affecting its interaction with E2 and assembly at the origin
in vivo
. Microscopy studies revealed that p80 is relocalized from the cytoplasm to discrete subnuclear foci by E1 and E2. Chromatin immunoprecipitation assays further revealed that p80 is recruited to the viral origin in an E1- and E2-dependent manner. Interestingly, overexpression of a 40-amino-acid-long p80-binding peptide, derived from HPV31 E1, was found to inhibit viral DNA replication by preventing the recruitment of endogenous p80 to the origin. Mutant peptides defective for p80 interaction were not inhibitory, demonstrating the specificity of this effect. Characterization of this E1 peptide by nuclear magnetic resonance (NMR) showed that it is intrinsically disordered in solution, while mapping studies indicated that the WD repeats of p80 are required for E1 interaction. These results provide additional evidence for the requirement for p80 in anogenital HPV DNA replication and highlight the potential of E1-p80 interaction as a novel antiviral target.
Tissue Exit: a Novel Control Point in the Accumulation of Antigen-Specific CD8 T Cells in the Influenza A Virus-Infected Lung
Authors: Jennrich Silke , Lee Michael H. , Lynn Rachel C. , Dewberry Kristofer , Debes Gudrun F. 
Published: January 2012

ABSTRACTMemory/effector T cells efficiently migrate into extralymphoid tissues and sites of infection, providing immunosurveillance and a first line of defense against invading pathogens. Even though it is a potential means to regulate the size, quality, and duration of a tissue infiltrate, T cell egress from infected tissues is poorly understood. Using a mouse model of influenza A virus infection, we found that CD8 effector T cells egressed from the infected lung in a CCR7-dependent manner. In contrast, following antigen recognition, effector CD8 T cell egress decreased and CCR7 function was reducedin vivoandin vitro, indicating that the exit of CD8 T cells from infected tissues is tightly regulated. Our data suggest that the regulation of T cell egress is a mechanism to retain antigen-specific effectors at the site of infection to promote viral clearance, while decreasing the numbers of bystander T cells and preventing overt inflammation.
Differential Gag-Specific Polyfunctional T Cell Maturation Patterns in HIV-1 Elite Controllers
Authors: Ferrando-Martínez Sara , Casazza Joseph P. , Leal Manuel , Machmach Kawthar , Muñoz-Fernández Ma Ángeles , Viciana Pompeyo , Koup Richard A. , Ruiz-Mateos Ezequiel 
Published: January 2012

ABSTRACT

A small fraction of HIV-infected individuals (<1%), referred to as elite controllers (EC), are able to maintain undetectable viral loads indefinitely without treatment. The role of the maturational phenotype of T cells in the control of HIV infection in these individuals is not well described. We compared the maturational and functional phenotypes of Gag-specific CD4 and CD8 T cells from EC, who maintain undetectable viral loads without treatment; relative controllers (RC), who maintain viral loads of <1,000 copies/ml without treatment; and noncontrollers (NC), who fail to control viral replication. EC maintained higher frequencies of HIV-specific CD4 T cells, less mature polyfunctional Gag-specific CD4 T cells (CD27
+
CD57
−
CD45RO
+
), and Gag-specific polyfunctional CD4 T cells than those observed in NC. In EC, the frequency of polyfunctional Gag-specific CD8 T cells was higher than that observed in RC and NC. RC had a similar functional phenotype to that observed in NC, despite consistently lower viral loads. Finally, we found a direct correlation between the frequency of Gag-specific CD27
+
CD57
−
CD45RO
+
CD4
+
T cells and the frequency of mature HIV-specific CD8 T cells. Altogether, our data suggest that immature Gag-specific interleukin-2 (IL-2)-producing CD4
+
T cells may play an important role in spontaneous control of HIV viremia by effectively supporting HIV-specific CD8 T lymphocytes. This difference appears to differentiate EC from RC.
Partitioning the Genetic Diversity of a Virus Family: Approach and Evaluation through a Case Study of Picornaviruses
Authors: Lauber Chris , Gorbalenya Alexander E. 
Published: January 2012

ABSTRACT
The recent advent of genome sequences as the only source available to classify many newly discovered viruses challenges the development of virus taxonomy by expert virologists who traditionally rely on extensive virus characterization. In this proof-of-principle study, we address this issue by presenting a computational approach (DEmARC) to classify viruses of a family into groups at hierarchical levels using a sole criterion—intervirus genetic divergence. To quantify genetic divergence, we used pairwise evolutionary distances (PEDs) estimated by maximum likelihood inference on a multiple alignment of family-wide conserved proteins. PEDs were calculated for all virus pairs, and the resulting distribution was modeled via a mixture of probability density functions. The model enables the quantitative inference of regions of distance discontinuity in the family-wide PED distribution, which define the levels of hierarchy. For each level, a limit on genetic divergence, below which two viruses join the same group, was objectively selected among a set of candidates by minimizing violations of intragroup PEDs to the limit. In a case study, we applied the procedure to hundreds of genome sequences of picornaviruses and extensively evaluated it by modulating four key parameters. It was found that the genetics-based classification largely tolerates variations in virus sampling and multiple alignment construction but is affected by the choice of protein and the measure of genetic divergence. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3905–3915, 2012), we analyze the substantial insight gained with the genetics-based classification approach by comparing it with the expert-based picornavirus taxonomy.
Toward Genetics-Based Virus Taxonomy: Comparative Analysis of a Genetics-Based Classification and the Taxonomy of Picornaviruses
Authors: Lauber Chris , Gorbalenya Alexander E. 
Published: January 2012

ABSTRACT

Virus taxonomy has received little attention from the research community despite its broad relevance. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3890–3904, 2012), we have introduced a quantitative approach to hierarchically classify viruses of a family using pairwise evolutionary distances (PEDs) as a measure of genetic divergence. When applied to the six most conserved proteins of the
Picornaviridae
, it clustered 1,234 genome sequences in groups at three hierarchical levels (to which we refer as the “GENETIC classification”). In this study, we compare the GENETIC classification with the expert-based picornavirus taxonomy and outline differences in the underlying frameworks regarding the relation of virus groups and genetic diversity that represent, respectively, the structure and content of a classification. To facilitate the analysis, we introduce two novel diagrams. The first connects the genetic diversity of taxa to both the PED distribution and the phylogeny of picornaviruses. The second depicts a classification and the accommodated genetic diversity in a standardized manner. Generally, we found striking agreement between the two classifications on species and genus taxa. A few disagreements concern the species
Human rhinovirus A
and
Human rhinovirus C
and the genus
Aphthovirus
, which were split in the GENETIC classification. Furthermore, we propose a new supergenus level and universal, level-specific PED thresholds, not reached yet by many taxa. Since the species threshold is approached mostly by taxa with large sampling sizes and those infecting multiple hosts, it may represent an upper limit on divergence, beyond which homologous recombination in the six most conserved genes between two picornaviruses might not give viable progeny.
Endovascular treatment of fusiform intracranial aneurysms
Authors: Devulapalli Kavi K , Chowdhry Shakeel A , Bambakidis Nicholas C , Selman Warren , Hsu Daniel Pierce 
Published: January 2012

Background and purposeEndovascular treatment (EVT) has emerged as an alternative therapeutic strategy for the treatment of intracranial fusiform aneurysms (IFAs), but little is known about the safety and efficacy of deconstructive and reconstructive methods, especially in patients presenting with subarachnoid hemorrhage (SAH). The purpose of this study is to describe the radiological and clinical outcomes in patients with IFAs undergoing EVT.MethodsA retrospective analysis was conducted of 18 patients undergoing EVT of IFAs, 13 of whom (72.2%) presented with SAH. Radiological outcomes were characterized by the presence of parent vessel opacification and aneurysmal remnants for patients undergoing deconstructive and reconstructive EVT, respectively. Clinical outcomes were characterized by the Glasgow Outcome Scale. Contingency analysis of factors associated with clinical outcomes in patients with ruptured aneurysms was conducted.ResultsTechnical success was achieved in 17 of the 18 patients (94.4%), with 10 (55.6%) undergoing reconstructive EVT and eight (44.4%) undergoing deconstructive EVT. For patients with SAH, favorable clinical outcomes were achieved in 9/13 (69.2%), with 3/6 (50.0%) undergoing reconstructive EVT and 6/7 (85.7%) undergoing deconstructive EVT. Among patients with ruptured aneurysms, only Hunt–Hess grade ≥3 was associated with an unfavorable clinical outcome (p=0.007). Favorable clinical outcomes were seen in all five patients with unruptured aneurysms.ConclusionBoth deconstructive and reconstructive EVT were found to be safe and effective in patients with unruptured aneurysms. Reconstructive EVT may be associated with a higher incidence of poor clinical outcomes in patients presenting with high-grade SAH.
Endovascular therapy of acute ischemic stroke: report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery
Authors: Blackham K A , Meyers P M , Abruzzo T A , Alberquerque F C , Fiorella D , Fraser J , Frei D , Gandhi C D , Heck D V , Hirsch J A , Hsu D P , Jayaraman M , Narayanan S , Prestigiacomo C , Sunshine J L ,   on behalf of the Society for NeuroInterventional Surgery
Published: January 2012

ObjectiveTo summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke.MethodsRecommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.
Short- and long-term leakage through composite liners. The 7th Arthur Casagrande Lecture1This lecture was presented at the 14th Pan-American Conference on Soil Mechanics and Geotechnical Engineering, Toronto, Ont., October 2011, and a pre-print appeared in the conference proceedings.
Authors: Rowe R. Kerry 
Published: January 2012

The factors that may affect short-term leakage through composite liners are examined. It is shown that the leakage through composite liners is only a very small fraction of that expected for either a geomembrane (GM) or clay liner (CL) alone. However, the calculated leakage through holes in a GM in direct contact with a clay liner is typically substantially smaller than that actually observed in the field. It is shown that calculated leakage taking account of typical connected wrinkle lengths observed in the field explains the observed field leakage through composite liners. Provided that care is taken to avoid excessive connected wrinkle lengths, the leakage through composite liners is very small compared to a typical GM or CL alone. It is shown that the leakage through composite liners with a geosynthetic clay liner (GCL) is typically much less than for composite liners with a compacted clay liner (CCL). Finally, factors that will affect long-term leakage through composite liners are discussed. It is concluded that composite liners have performed extremely well in field applications for a couple of decades and that recent research both helps understand why they have worked so well and provides new insight into issues that need to be considered to ensure excellent long-term liner performance of composite liners — especially for applications where the liner temperature can exceed about 35 °C.
The Natural History of Preclinical Diastolic Dysfunction
Authors: Vogel Mark W. , Slusser Joshua P. , Hodge David O. , Chen Horng H. 
Published: January 2012

Background—
Preclinical diastolic dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF) and with normal systolic function. Our objective was to determine the risk factors associated with the progression from PDD (stage B) HF to symptomatic (stage C) HF.

Methods and Results—

Using the resources of the Rochester Epidemiology Project, all residents of Olmsted County, MN, who underwent echocardiography between January 1, 2004, and December 31, 2005, and had grade 2–4 diastolic dysfunction and ejection fraction ≥50% were identified. Patients with a diagnosis of HF before or within 30 days of the echocardiogram were excluded. Patients were also excluded if they had a diagnosis of atrial fibrillation or severe mitral or aortic valve regurgitation at the time of the echocardiogram. A total of 388 patients met the inclusion criteria. The mean age of the cohort was 67±12 years, with a female (57%) predominance. Prevalence of renal insufficiency (estimated glomerular filtration rate <60 mL/min per 1.73 m
2
) was 34%. The 3-year cumulative probabilities of development of (stage C) HF, development of atrial fibrillation, cardiac hospitalization, and mortality were 11.6%, 14.5%, 17.7%, and 10.1% respectively. In multivariable Cox proportional hazard regression analysis, we determined that age, renal dysfunction, and right ventricular systolic pressure were independently associated with the development of HF.

Conclusions—
This population-based study demonstrated that in PDD (stage B) HF, there was a moderate degree of progression to symptomatic (stage C) HF over 3 years, and renal dysfunction was associated with this progression independent of age, sex, hypertension, coronary disease, and ejection fraction.
A Simple Model for Stratocumulus to Shallow Cumulus Cloud Transitions
Authors: Chung D. , Teixeira J. 
Published: January 2012

Abstract
It is shown that essential features of stratocumulus to shallow cumulus cloud transitions can be represented by a simple stochastic model constructed from an ensemble of transitions, each of which depends on the amount of surface latent heat flux relative to initial cloud-top longwave net radiative flux. In its essence the simple model establishes a causal relation between the increase of sea surface temperature (SST) and the decrease in cloud fraction (CF) along the trade winds. The mean and variance of SST are taken from observations. Model predictions are compared with observations of CF along Lagrangian trajectories in four eastern subtropical ocean regions. The model reproduces well the decrease in mean CF and the peak in CF spread.
Evaluation and Intercomparison of Cloud Fraction and Radiative Fluxes in Recent Reanalyses over the Arctic Using BSRN Surface Observations
Authors: Zib Behnjamin J. , Dong Xiquan , Xi Baike , Kennedy Aaron 
Published: January 2012

Abstract
With continual advancements in data assimilation systems, new observing systems, and improvements in model parameterizations, several new atmospheric reanalysis datasets have recently become available. Before using these new reanalyses it is important to assess the strengths and underlying biases contained in each dataset. A study has been performed to evaluate and compare cloud fractions (CFs) and surface radiative fluxes in several of these latest reanalyses over the Arctic using 15 years (1994–2008) of high-quality Baseline Surface Radiation Network (BSRN) observations from Barrow (BAR) and Ny-Alesund (NYA) surface stations. The five reanalyses being evaluated in this study are (i) NASA's Modern-Era Retrospective analysis for Research and Applications (MERRA), (ii) NCEP's Climate Forecast System Reanalysis (CFSR), (iii) NOAA's Twentieth Century Reanalysis Project (20CR), (iv) ECMWF's Interim Reanalysis (ERA-I), and (v) NCEP–Department of Energy (DOE)'s Reanalysis II (R2). All of the reanalyses show considerable bias in reanalyzed CF during the year, especially in winter. The large CF biases have been reflected in the surface radiation fields, as monthly biases in shortwave (SW) and longwave (LW) fluxes are more than 90 (June) and 60 W m−2 (March), respectively, in some reanalyses. ERA-I and CFSR performed the best in reanalyzing surface downwelling fluxes with annual mean biases less than 4.7 (SW) and 3.4 W m−2 (LW) over both Arctic sites. Even when producing the observed CF, radiation flux errors were found to exist in the reanalyses suggesting that they may not always be dependent on CF errors but rather on variations of more complex cloud properties, water vapor content, or aerosol loading within the reanalyses.
The Role of Barents Sea Ice in the Wintertime Cyclone Track and Emergence of a Warm-Arctic Cold-Siberian Anomaly
Authors: Inoue Jun , Hori Masatake E. , Takaya Koutarou 
Published: January 2012

AbstractSea ice variability over the Barents Sea with its resultant atmospheric response has been considered one of the triggers of unexpected downstream climate change. For example, East Asia has experienced several major cold events while the underlying temperature over the Arctic has risen steadily. To understand the influence of sea ice in the Barents Sea on atmospheric circulation during winter from a synoptic perspective, this study evaluated the downstream response in cyclone activities with respect to the underlying sea ice variability. The composite analysis, including all cyclone events over the Nordic seas, revealed that an anticyclonic anomaly prevailed along the Siberian coast during light ice years over the Barents Sea. This likely caused anomalous warm advection over the Barents Sea and cold advection over eastern Siberia. The difference in cyclone paths between heavy and light ice years was expressed as a warm-Arctic cold-Siberian (WACS) anomaly. The lower baroclinicity over the Barents Sea during the light ice years, which resulted from a weak gradient in sea surface temperature, prevented cyclones from traveling eastward. This could lead to fewer cyclones and hence to an anticyclonic anomaly over the Siberian coast.