bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphotoxin Alpha-Deficient Mice Clear Persistent Rotavirus Infection after Local Generation of Mucosal IgA
Authors: Lopatin Uri , Blutt Sarah E. , Conner Margaret E. , Kelsall Brian L. 
Published: October 2012

ABSTRACTRotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LTα−/−) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα−/−and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LTα−/−mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LTα−/−mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LTα-independent manner.
Molecular Requirements for T Cell Recognition of N-Myristoylated Peptides Derived from the Simian Immunodeficiency Virus Nef Protein
Authors: Morita Daisuke , Yamamoto Yukie , Suzuki Juri , Mori Naoki , Igarashi Tatsuhiko , Sugita Masahiko 
Published: October 2012

ABSTRACT

We have recently isolated a rhesus macaque cytotoxic T cell line, 2N5.1, that specifically recognizes an N-myristoylated 5-mer peptide (C
14
-Gly-Gly-Ala-Ile-Ser [C14nef5]) derived from the simian immunodeficiency virus (SIV) Nef protein. Such C14nef5-specific T cells expand in the circulation of SIV-infected monkeys, underscoring the capacity of T cells to recognize viral lipopeptides; however, the molecular basis for the lipopeptide antigen presentation remains to be elucidated. Here, functional studies indicated that the putative antigen-presenting molecule for 2N5.1 was likely to have two separate antigen-binding sites, one for interaction with a C
14
-saturated acyl chain and the other for anchorage of the C-terminal serine residue. Mutants with alanine substitutions for the second glycine residue and the fourth isoleucine residue were not recognized by 2N5.1 but interfered with the presentation of C14nef5 to 2N5.1, indicating that these structural analogues retained the ability to interact with the antigen-presenting molecules. In contrast to the highly specific recognition of C14nef5 by 2N5.1, an additional cytotoxic T cell line, SN45, established independently from a C14nef5-stimulated T cell culture, showed superb reactivity to both C14nef5 and an N-myristoylated Nef 4-mer peptide, and therefore, the C-terminal serine residue was dispensable for the recognition of lipopeptides by the SN45 T cells. Furthermore, the mutants with alanine substitutions were indeed recognized by the SN45 T cells. Given that N-myristoylation of the Nef protein occurs in the conserved motifs and is critical for viral pathogenesis, these observations predict that the lipopeptide-specific T cell response is difficult for viruses to avoid by simply introducing amino acid mutations.
Genomic Characterization of Japanese Macaque Rhadinovirus, a Novel Herpesvirus Isolated from a Nonhuman Primate with a Spontaneous Inflammatory Demyelinating Disease
Authors: Estep Ryan D. , Hansen Scott G. , Rogers Kelsey S. , Axthelm Michael K. , Wong Scott W. 
Published: October 2012

ABSTRACT

Japanese macaque rhadinovirus (JMRV) is a novel gamma-2 herpesvirus that was isolated from a Japanese macaque (JM) with an inflammatory demyelinating encephalomyelitis referred to as Japanese macaque encephalomyelitis, a disease that possesses clinical and histopathological features resembling multiple sclerosis in humans. Genomic DNA sequence analysis reveals that JMRV is a gammaherpesvirus closely related to rhesus macaque rhadinovirus (RRV) and human herpesvirus 8. We describe here the complete nucleotide sequence and structure of the JMRV genome, as well as the sequence of two plaque isolates of this virus. Analysis of the JMRV genome not only demonstrates that this virus shares a number of genes with RRV that may be involved in pathogenesis but also indicates the presence of unique JMRV genes that could potentially contribute to disease development. The knowledge of the genomic sequence of JMRV, and the ability to easily propagate the virus
in vitro
, make JMRV infection of JM an attractive model for examining the potential role of an infectious viral agent in the development of demyelinating encephalomyelitis disease
in vivo
.
Deep RNA Sequencing Reveals Complex Transcriptional Landscape of a Bat Adenovirus
Authors: Wu Lijun , Zhou Peng , Ge Xingyi , Wang Lin-Fa , Baker Michelle L. , Shi Zhengli 
Published: October 2012

ABSTRACT
Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages, the early-stage genes encoding mainly host interaction proteins, the intermediate-stage genes for the DNA replication and assembly proteins, and the late-stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from those of their counterpart genes previously reported for human AdV type 2. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel bat AdV and the virus-host interactions which will be useful for the understanding and investigation of AdV replication, pathogenesis, and specific virus-bat interactions in future research.
ADP Ribosylation Factor 1 Plays an Essential Role in the Replication of a Plant RNA Virus
Authors: Hyodo Kiwamu , Mine Akira , Taniguchi Takako , Kaido Masanori , Mise Kazuyuki , Taniguchi Hisaaki , Okuno Tetsuro 
Published: October 2012

ABSTRACTEukaryotic positive-strand RNA viruses replicate using the membrane-bound replicase complexes, which contain multiple viral and host components. Virus infection induces the remodeling of intracellular membranes. Virus-induced membrane structures are thought to increase the local concentration of the components that are required for replication and provide a scaffold for tethering the replicase complexes. However, the mechanisms underlying virus-induced membrane remodeling are poorly understood. RNA replication of red clover necrotic mosaic virus (RCNMV), a positive-strand RNA plant virus, is associated with the endoplasmic reticulum (ER) membranes, and ER morphology is perturbed in RCNMV-infected cells. Here, we identified ADP ribosylation factor 1 (Arf1) in the affinity-purified RCNMV RNA-dependent RNA polymerase fraction. Arf1 is a highly conserved, ubiquitous, small GTPase that is implicated in the formation of the coat protein complex I (COPI) vesicles on Golgi membranes. Usingin vitropulldown and bimolecular fluorescence complementation analyses, we showed that Arf1 interacted with the viral p27 replication protein within the virus-induced large punctate structures of the ER membrane. We found that inhibition of the nucleotide exchange activity of Arf1 using the inhibitor brefeldin A (BFA) disrupted the assembly of the viral replicase complex and p27-mediated ER remodeling. We also showed that BFA treatment and the expression of dominant negative Arf1 mutants compromised RCNMV RNA replication in protoplasts. Interestingly, the expression of a dominant negative mutant of Sar1, a key regulator of the biogenesis of COPII vesicles at ER exit sites, also compromised RCNMV RNA replication. These results suggest that the replication of RCNMV depends on the host membrane traffic machinery.
The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition
Authors: Jiang Xiaofeng , Zhou Jun , Giobbie-Hurder Anita , Wargo Jennifer , Hodi F. Stephen 
Published: October 2012

Abstract
Purpose: Selective BRAF inhibition (BRAFi) provides a paradigm shift for melanoma treatment. The duration of benefit is typically limited before resistance develops. Interest remains in combining targeted and immune therapies to overcome resistance and improve durability of clinical benefit. One mechanism of evading immune destruction is programmed death-1-ligand 1 (PD-L1) expression by tumors that results in potent antitumor immune suppression.
Experimental Design: BRAFi-resistant melanoma cells were examined for changes in PD-L1 expression by immunoblot and flow cytometry. Signaling pathways involved in altering PD-L1 expression were examined. Strategies to maximize the effect of the BRAFi therapy were studied including MEKi, MEKi combinations, and additional pathways including phosphoinositide-3 kinase (PI3K).
Results: Melanoma cells resistant to BRAFi exhibit increased MAPK signaling and promotion of PD-L1 expression. PD-L1 expression is transcriptionally modulated by c-Jun and augmented by STAT3. MEK inhibition (MEKi) regains downregulation of MAPK signaling and suppresses the production of PD-L1. MEKi in melanoma cells shows dual therapeutic effects with simultaneous suppression of PD-L1 expression and induction of apoptosis. By combining MEKi with BRAFi, an additive effect on the inhibition of PD-L1 expression results.
Conclusions: We report a novel mechanism that suppresses preexisting immune responses in patients with melanoma receiving BRAFi therapy. BRAFi resistance leads to increased expression of PD-L1 in melanoma cells, mediated by c-Jun and STAT3. MEKi may be feasible to counteract BRAFi resistance of MAPK reactivation and also for the additive effect of PD-L1 suppression. Potential therapeutic benefits of combining targeted inhibitors and immune modulation to improve patient outcomes should be investigated. Clin Cancer Res; 19(3); 598–609. ©2012 AACR.
Surface Irradiances Consistent with CERES-Derived Top-of-Atmosphere Shortwave and Longwave Irradiances
Authors: Kato Seiji , Loeb Norman G. , Rose Fred G. , Doelling David R. , Rutan David A. , Caldwell Thomas E. , Yu Lisan , Weller Robert A. 
Published: October 2012

Abstract
The estimate of surface irradiance on a global scale is possible through radiative transfer calculations using satellite-retrieved surface, cloud, and aerosol properties as input. Computed top-of-atmosphere (TOA) irradiances, however, do not necessarily agree with observation-based values, for example, from the Clouds and the Earth’s Radiant Energy System (CERES). This paper presents a method to determine surface irradiances using observational constraints of TOA irradiance from CERES. A Lagrange multiplier procedure is used to objectively adjust inputs based on their uncertainties such that the computed TOA irradiance is consistent with CERES-derived irradiance to within the uncertainty. These input adjustments are then used to determine surface irradiance adjustments. Observations by the Atmospheric Infrared Sounder (AIRS), Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), CloudSat, and Moderate Resolution Imaging Spectroradiometer (MODIS) that are a part of the NASA A-Train constellation provide the uncertainty estimates. A comparison with surface observations from a number of sites shows that the bias [root-mean-square (RMS) difference] between computed and observed monthly mean irradiances calculated with 10 years of data is 4.7 (13.3) W m−2 for downward shortwave and −2.5 (7.1) W m−2 for downward longwave irradiances over ocean and −1.7 (7.8) W m−2 for downward shortwave and −1.0 (7.6) W m−2 for downward longwave irradiances over land. The bias and RMS error for the downward longwave and shortwave irradiances over ocean are decreased from those without constraint. Similarly, the bias and RMS error for downward longwave over land improves, although the constraint does not improve downward shortwave over land. This study demonstrates how synergetic use of multiple instruments (CERES, MODIS, CALIPSO, CloudSat, AIRS, and geostationary satellites) improves the accuracy of surface irradiance computations.
Climate Feedbacks in CCSM3 under Changing CO2 Forcing. Part II: Variation of Climate Feedbacks and Sensitivity with Forcing
Authors: Jonko Alexandra K. , Shell Karen M. , Sanderson Benjamin M. , Danabasoglu Gokhan 
Published: October 2012

Abstract
Are equilibrium climate sensitivity and the associated radiative feedbacks a constant property of the climate system, or do they change with forcing magnitude and base climate? Using the radiative kernel technique, feedbacks and climate sensitivity are evaluated in a fully coupled general circulation model (GCM) for three successive doublings of carbon dioxide starting from present-day concentrations. Climate sensitivity increases by 23% between the first and third CO2 doublings. Increases in the positive water vapor and cloud feedbacks are partially balanced by a decrease in the positive surface albedo feedback and an increase in the negative lapse rate feedback. Feedbacks can be decomposed into a radiative flux change and a climate variable response to temperature change. The changes in water vapor and Planck feedbacks are due largely to changes in the radiative response with climate state. Higher concentrations of greenhouse gases and higher temperatures lead to more absorption and emission of longwave radiation. Changes in cloud feedbacks are dominated by the climate response to temperature change, while the lapse rate and albedo feedbacks combine elements of both. Simulations with a slab ocean model (SOM) version of the GCM are used to verify whether an SOM-GCM accurately reproduces the behavior of the fully coupled model. Although feedbacks differ in magnitude between model configurations (with differences as large as those between CO2 doublings for some feedbacks), changes in feedbacks between CO2 doublings are consistent in sign and magnitude in the SOM-GCM and the fully coupled model.
Seasonal Prediction of Arctic Sea Ice Extent from a Coupled Dynamical Forecast System
Authors: Wang Wanqiu , Chen Mingyue , Kumar Arun 
Published: October 2012

Abstract
While fully coupled atmosphere–ocean models have been used to study the seasonal predictability of sea ice variations within the context of models’ own variability, their capability in predicting the observed sea ice at the seasonal time scales is not well assessed. In this study, sea ice predictions from the recently developed NCEP Climate Forecast System, version 2 (CFSv2), a fully coupled atmosphere–ocean model including an interactive dynamical sea ice component, are analyzed. The focus of the analysis is the performance of CFSv2 in reproducing observed Northern Hemisphere sea ice extent (SIE). The SIE climatology, long-term trend, interannual variability, and predictability are assessed. CFSv2 contains systematic biases that are dependent more on the forecast target month than the initial month, with a positive SIE bias for the forecast for January–September and a negative SIE bias for the forecast for October–December. A large source of seasonal prediction skill is from the long-term trend, which is underestimated in the CFSv2. Prediction skill of interannual SIE anomalies is found to be primarily within the first three target months and is largest in the summer and early fall. The performance of the prediction of sea ice interannual variations varies from year to year and is found to be related to initial sea ice thickness. Potential predictability based on the forecast ensemble, its dependence on model deficiencies, and implications of the results from this study for improvements in the seasonal sea ice prediction are discussed.
Tropical Cyclone Formation Guidance Using Pregenesis Dvorak Climatology. Part I: Operational Forecasting and Predictive Potential
Authors: Cossuth Joshua H. , Knabb Richard D. , Brown Daniel P. , Hart Robert E. 
Published: October 2012

Abstract
While there are a variety of modes for tropical cyclone (TC) development, there have been relatively few efforts to systematically catalog both nondeveloping and developing cases. This paper introduces an operationally derived climatology of tropical disturbances that were analyzed using the Dvorak technique at the National Hurricane Center (NHC) and the Central Pacific Hurricane Center from 2001 to 2011. Using these Dvorak intensity estimates, the likelihood of genesis is calculated as a historical baseline for TC prediction. Despite the limited period of record, the climatology of Dvorak analyses of incipient tropical systems has a spatial distribution that compares well with previous climatologies. The North Atlantic basin shows substantial regional variability in Dvorak classification frequency. In contrast, tropical disturbances in the combined eastern and central North Pacific basins (which split at 125°W into an eastern region and a central region) have a single broad frequency maximum and limited meridional extent. When applied to forecasting, several important features are discovered. Dvorak fixes are sometimes unavailable for disturbances that develop into TCs, especially at longer lead times. However, when probabilities of genesis are calculated by a Dvorak current intensity (CI) number, the likelihood stratifies well by basin and intensity. Tropical disturbances that are analyzed as being stronger (a higher Dvorak CI number) achieve genesis more often. Further, all else being equal, genesis rates are highest in the eastern Pacific, followed by the Atlantic. Out-of-sample verification of predictive skill shows comparable results to that of the NHC, with potential to inform forecasts and provide the first disturbance-centric baseline for tropical cyclogenesis potential.
Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats
Authors: Aktas Cevat , Kanter Mehmet , Erboga Mustafa , Mete Rafet , Oran Mustafa 
Published: October 2012

The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress.
CXC chemokine ligand 12/Stromal cell-derived factor-1 regulates cell adhesion in human colon cancer cells by induction of intercellular adhesion molecule-1
Authors: Tung Shui-Yi , Chang Shun-Fu , Chou Ming-Hui , Huang Wen-Shih , Hsieh Yung-Yu , Shen Chien-Heng , Kuo Hsing-Chun , Chen Cheng-Nan 
Published: October 2012

AbstractBackgroundThe CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) and CXC receptor 4 (CXCR4) axis is involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. Interaction between CRC cells and endothelium is a key event in tumor progression. The aim of this study was to investigate the effect of SDF-1 on the adhesion of CRC cells.MethodsHuman CRC DLD-1 cells were used to study the effect of SDF-1 on intercellular adhesion molecule-1 (ICAM-1) expression and cell adhesion to endothelium.ResultsSDF-1 treatment induced adhesion of DLD-1 cells to the endothelium and increased the expression level of the ICAM-1. Inhibition of ICAM-1 by small interfering RNA (siRNA) and neutralizing antibody inhibited SDF-1-induced cell adhesion. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK, JNK and p38 pathways is critical for SDF-1-induced ICAM-1 expression and cell adhesion. Promoter activity and transcription factor ELISA assays showed that SDF-1 increased Sp1-, C/EBP-β- and NF-κB-DNA binding activities in DLD-1 cells. Inhibition of Sp1, C/EBP-β and NF-κB activations by specific siRNA blocked the SDF-1-induced ICAM-1 promoter activity and expression. The effect of SDF-1 on cell adhesion was mediated by the CXCR4.ConclusionOur findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.
Malaria research challenges in low prevalence settings
Authors: Stresman Gillian , Kobayashi Tamaki , Kamanga Aniset , Thuma Philip E , Mharakurwa Sungano , Moss William J , Shiff Clive 
Published: October 2012

Abstract
The prevalence of malaria has reduced significantly in some areas over the past decade. These reductions have made local elimination possible and the research agenda has shifted to this new priority. However, there are critical issues that arise when studying malaria in low transmission settings, particularly identifying asymptomatic infections, accurate detection of individuals with microparasitaemic infections, and achieving a sufficient sample size to have an adequately powered study. These challenges could adversely impact the study of malaria elimination if they remain unanswered.