bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway
Authors: Fabozzi Giulia , Nabel Christopher S. , Dolan Michael A. , Sullivan Nancy J. 
Published: January 2011

ABSTRACT
Cellular RNA interference (RNAi) provides a natural response against viral infection, but some viruses have evolved mechanisms to antagonize this form of antiviral immunity. To determine whether Ebolavirus (EBOV) counters RNAi by encoding suppressors of RNA silencing (SRSs), we screened all EBOV proteins using an RNAi assay initiated by exogenously delivered small interfering RNAs (siRNAs) against either an EBOV or a reporter gene. In addition to viral protein 35 (VP35), we found that VP30 and VP40 independently act as SRSs. Here, we present the molecular mechanisms of VP30 and VP35. VP30 interacts with Dicer independently of siRNA and with one Dicer partner, TRBP, only in the presence of siRNA. VP35 directly interacts with Dicer partners TRBP and PACT in an siRNA-independent fashion and in the absence of effects on interferon (IFN). Taken together, our findings elucidate a new mechanism of RNAi suppression that extends beyond the role of SRSs in double-stranded RNA (dsRNA) binding and IFN antagonism. The presence of three suppressors highlights the relevance of host RNAi-dependent antiviral immunity in EBOV infection and illustrates the importance of RNAi in shaping the evolution of RNA viruses.
Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model
Authors: Khong Wei Xin , Foo Damian G. W. , Trasti Scott L. , Tan Eng Lee , Alonso Sylvie 
Published: January 2011

ABSTRACTEnterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD) in young children and has been consistently associated with the most severe complications of the disease, including central nervous system inflammation and pulmonary edema. Increasing frequency and amplitude of EV71 outbreaks have raised awareness and concerns worldwide. Previous reports proposed that overwhelming virus replication combined with the induction of massive proinflammatory cytokines is responsible for the pathogenicity of EV71. Specifically, elevated interleukin-6 (IL-6) levels were observed consistently in patients and strongly correlated with disease severity. In this study, we show in the neonate mouse model that sustained high levels of IL-6 produced upon EV71 infection lead to severe tissue damage and eventually death of the animals. Administration of anti-IL-6 neutralizing antibodies after the onset of the clinical symptoms successfully improved the survival rates and clinical scores of the infected hosts. Compared to untreated infected controls, anti-IL-6-treated mice displayed reduced tissue damage, absence of splenic atrophy, and increased immune cell activation. In addition, markedly elevated systemic levels of IL-10 were measured in the protected animals. Furthermore, there was no significant difference in virus titers between anti-IL-6-treated mice and untreated mice, indicating that the anti-IL-6 antibody-mediated protection is independent of the virus load. Our findings thus demonstrate that IL-6 plays a major role in EV71-induced immunopathogenesis. As there is still neither vaccine nor treatment available against EV71, anti-IL-6 antibody treatment represents a potential therapeutic approach to providing protection from the most severe complications of the disease.
The Role of Aldehyde Dehydrogenase and Hsp70 in Suppression of White Spot Syndrome Virus Replication at High Temperature
Authors: Lin Ying-Ru , Hung Hsiao-Chun , Leu Jiann-Horng , Wang Hao-Ching , Kou Guang-Hsiung , Lo Chu-Fang 
Published: January 2011

ABSTRACT

High temperature (32 to 33°C) has been shown to reduce mortality in white spot syndrome virus (WSSV)-infected shrimps, but the mechanism still remains unclear. Here we show that in WSSV-infected shrimps cultured at 32°C, transcriptional levels of representative immediate-early, early, and late genes were initially higher than those at 25°C. However, neither the IE1 nor VP28 protein was detected at 32°C, suggesting that high temperature might inhibit WSSV protein synthesis. Two-dimensional gel electrophoresis analysis revealed two proteins, NAD-dependent aldehyde dehydrogenase (ALDH) and the proteasome alpha 4 subunit (proteasome α4), that were markedly upregulated in WSSV-infected shrimps at 32°C. Reverse transcription-PCR (RT-PCR) analysis of members of the heat shock protein family also showed that
hsp70
was upregulated at 32°C. When
aldh
,
proteasome α4
, and
hsp70
were knocked down by double-stranded RNA interference and shrimps were challenged with WSSV, the
aldh
and
hsp70
knockdown shrimps became severely infected at 32°C, while the
proteasome α4
knockdown shrimps remained uninfected. Our results therefore suggest that ALDH and Hsp70 both play an important role in the inhibition of WSSV replication at high temperature.
Glycosylphosphatidylinositol Anchor-Dependent Stimulation Pathway Required for Generation of Baculovirus-Derived Recombinant Scrapie Prion Protein
Authors: Imamura Morikazu , Kato Nobuko , Yoshioka Miyako , Okada Hiroyuki , Iwamaru Yoshifumi , Shimizu Yoshihisa , Mohri Shirou , Yokoyama Takashi , Murayama Yuichi 
Published: January 2011

ABSTRACT

The pathogenic isoform (PrP
Sc
) of the host-encoded cellular prion protein (PrP
C
) is considered to be an infectious agent of transmissible spongiform encephalopathy (TSE). The detailed mechanism by which the PrP
Sc
seed catalyzes the structural conversion of endogenous PrP
C
into nascent PrP
Sc
in vivo
still remains unclear. Recent studies reveal that bacterially derived recombinant PrP (recPrP) can be used as a substrate for the
in vitro
generation of protease-resistant recPrP (recPrP
res
) by protein-misfolding cyclic amplification (PMCA). These findings imply that PrP modifications with a glycosylphosphatidylinositol (GPI) anchor and asparagine (N)-linked glycosylation are not necessary for the amplification and generation of recPrP
Sc
by PMCA. However, the biological properties of PrP
Sc
obtained by
in vivo
transmission of recPrP
res
are unique or different from those of PrP
Sc
used as the seed, indicating that the mechanisms mediated by these posttranslational modifications possibly participate in reproductive propagation of PrP
Sc
. In the present study, using baculovirus-derived recombinant PrP (Bac-PrP), we demonstrated that Bac-PrP is useful as a PrP
C
substrate for amplification of the mouse scrapie prion strain Chandler, and PrP
Sc
that accumulated in mice inoculated with Bac-PrP
res
had biochemical and pathological properties very similar to those of the PrP
Sc
seed. Since Bac-PrP modified with a GPI anchor and brain homogenate of
Prnp
knockout mice were both required to generate Bac-PrP
res
, the interaction of GPI-anchored PrP with factors in brain homogenates is essential for reproductive propagation of PrP
Sc
. Therefore, the Bac-PMCA technique appears to be extremely beneficial for the comprehensive understanding of the GPI anchor-mediated stimulation pathway.
Sensitivity of the Phadia EliA connective tissue disease screen for less common disease-specific autoantibodies
Authors: Parker Jennifer C , Bunn Christopher C 
Published: January 2011

AimTo evaluate the sensitivity of a commercial autoantibody screening method (Phadia EliA connective tissue disease (CTD) screen) for the detection of less common antibody specificities associated with connective tissue disease.Methods399 sera positive for anti-PM/Scl (n=102), anti-RNA polymerase III (n=199), anti-fibrillarin (n=50), anti-Mi-2 (n=12), anti-proliferating cell nuclear antigen (PCNA) (n=13) and anti-ribosomal P (n=23) were analysed using the solid phase assay. Each well was coated with the respective antigens for these autoantibodies and also with the antigens Ro, La, Jo-1, Scl-70, CENP-B, U1-RNP, Sm and native DNA.ResultsAll the anti-ribosomal P, anti-PCNA and anti-Mi-2 sera and 94% of the anti-PM/Scl sera were positive. For anti-fibrillarin, 36 (68%) were positive and 12 (22%) were equivocal. For anti-RNA polymerase III, 131 (67%) were positive, 23 (11%) were equivocal and 45 (22%) were negative.ConclusionsThe sensitivity of the Phadia EliA CTD screen is currently insufficient for the assay to be used as a screening test for anti-fibrillarin and anti-RNA polymerase III, but appears to be satisfactory for the other autoantibodies tested.
Geology, petrology and alteration geochemistry of the Palaeoproterozoic intrusive hosted Älgträsk Au deposit, Northern Sweden
Authors: Bejgarn Therese , Årebäck Hans , Weihed Pär , Nylander Juhani 
Published: January 2011

Abstract

The Älgträsk intrusive hosted Au deposit, Skellefte district, northern Sweden, is situated in the oldest, most heterogeneous part of the
c
. 1.89–1.86 Ga Jörn granitoid complex, which intruded a complex volcano–sedimentary succession in an island arc or continental margin arc environment. The Tallberg porphyry Cu deposit, situated only 3 km west of Älgträsk, is associated with quartz feldspar porphyritic dykes. These dykes are suggested to be genetically related to similar porphyry dykes in Älgträsk and the tonalitic host rock in Tallberg. The granodiorite hosting the Älgträsk Au-deposit does not appear to be genetically related to the tonalite or the porphyry dykes.
KPNA2 Expression Is an Independent Adverse Predictor of Biochemical Recurrence after Radical Prostatectomy
Authors: Mortezavi Ashkan , Hermanns Thomas , Seifert Hans-Helge , Baumgartner Martin K. , Provenzano Maurizio , Sulser Tullio , Burger Maximilian , Montani Matteo , Ikenberg Kristian , Hofstädter Ferdinand , Hartmann Arndt , Jaggi Rolf , Moch Holger , Kristiansen Glen , Wild Peter J. 
Published: January 2011

Abstract
Purpose: To analyze rates of expression of karyopherin alpha 2 (KPNA2) in different prostate tissues and to evaluate the prognostic properties for patients with primary prostate cancer.
Experimental Design: Tissue microarrays (TMA) contained 798 formalin-fixed, paraffin-embedded prostate tissue cores from two different institutes of pathology. TMAs were stained immunohistochemically for KPNA2 and NBS1. SiRNA technologies were used to inhibit KPNA2 expression in vitro, and the effect of this inhibition on cellular viability was determined. Efficiency of knockdown experiments was determined by Western blot analysis.
Results: KPNA2 expression was significantly upregulated in carcinomas of the prostate, especially in metastatic and castration-resistant prostate cancer samples. Positive nuclear KPNA2 immunoreactivity was identified as a novel predictor of biochemical recurrence after radical prostatectomy (n = 348), and was independent of the well-established predictive factors preoperative PSA value, Gleason score, tumor stage, and surgical margin status. These results were validated by analyzing a second and independent prostate cancer cohort (n = 330). Further, in vitro experiments showed that the cell proliferation and viability of PC3 cells was significantly reduced when KPNA2 expression was inhibited. KPNA2 knockdown did not induce PARP cleavage as marker for apoptosis. No significantly increased sub-G1 fraction could be found by FACS analysis.
Conclusions: KPNA2 is a novel independent prognostic marker for disease progression after radical prostatectomy. This allows to identify patients who need more aggressive treatment. It can moreover be speculated that patients not suited for surveillance regimens might be identified at initial biopsy by a positive KPNA2 immunohistochemistry. Clin Cancer Res; 17(5); 1111–21. ©2011 AACR.
Phase I Studies of CBP501, a G2 Checkpoint Abrogator, as Monotherapy and in Combination with Cisplatin in Patients with Advanced Solid Tumors
Authors: Shapiro Geoffrey I. , Tibes Raoul , Gordon Michael S. , Wong Bryan Y. , Eder Joseph Paul , Borad Mitesh J. , Mendelson David S. , Vogelzang Nicholas J. , Bastos Bruno R. , Weiss Glen J. , Fernandez Cristian , Sutherland William , Sato Hitoshi , Pierceall William E. , Weaver David , Slough Scott , Wasserman Ernesto , Kufe Donald W. , Von Hoff Daniel , Kawabe Takumi , Sharma Sunil 
Published: January 2011

AbstractPurpose: Two phase I dose-escalation studies were conducted to determine the maximum tolerated dose (MTD) and safety profile of the G2 checkpoint abrogator CBP501, as a single agent and in combination with cisplatin.Experimental Design: Patients with advanced solid tumors were treated with CBP501 alone (D1/D8/D15, q4w, from 0.9 mg/m2), or with cisplatin (both on D1, q3w, from 3.6 mg/m2 CBP501, 50 mg/m2 cisplatin). Dose escalation proceeded if dose-limiting toxicity (DLT) was observed in 1 or less of 3 to 6 patients; CBP501 dose increments were implemented according to the incidence of toxicity. MTD was determined from DLTs occurring during the first two cycles.Results: In the combination study, the DLT was a histamine-release syndrome (HRS) occurring 10 to 60 minutes after initiating infusion that was attenuated by prophylaxis comprising dexamethasone, diphenhydramine, ranitidine, and loratadine. The MTD was 25 mg/m2 CBP501 and 75 mg/m2 cisplatin, with two patients at the highest dose (36.4 mg/m2 CBP501, 75 mg/m2 cisplatin) experiencing grade 3 HRS. The only DLT with monotherapy was transient G3 rise of troponin in one patient. Grade 3 to 4 treatment–related events were rare. Promising activity was observed with CBP501/cisplatin, mainly in ovarian and mesothelioma patients who had previously progressed on platinum-containing regimens. Among ovarian cancer patients, low expression of DNA repair proteins was associated with partial response or stable disease.Conclusions: CBP501 is well tolerated in patients as monotherapy and with cisplatin. At the recommended phase II dose (RP2D), the combination is feasible and HRS manageable with prophylaxis. Evidence of antitumor activity was observed in platinum-resistant patients. Clin Cancer Res; 17(10); 3431–42. ©2011 AACR.
Contesting Famine: Hunger and Nutrition in Occupied Japan, 1945-1952
Authors: Aldous Chris 
Published: January 2011

AbstractThis article analyzes both the policy debates within the American Occupation over famine, food relief and nutrition in Occupied Japan (1945-52) and the contested terms in which the debate was conducted. Conflict arose over muddled accounting of food intake in calories, a rampant black market that suggested a failure of equitable distribution, and the absence of serious unrest despite imports falling short of minimal stated requirements. Occupation authorities questioned estimates made by the Japanese government. There was internal disagreement among American authorities in Japan and between interested parties in Washington, as well as among the Allies in the Far Eastern Commission. Herbert Hoover's Famine Emergency Committee of 1946 sounded an alarm, and the Food and Fertilizer Mission of February 1947 marked a shift away from rather crude quantitative measures of caloric intake to more subtle qualitative ones of dietary balance and combinations of nutrients. The Occupation's chief concern then became the dearth of animal protein. Attempts to correct this shortfall by reestablishing Japan's fishing and whaling industries proved unpopular with U.S. allies. The Occupation preferred to champion the success of its school lunch program, whose core component – powdered skim milk imported from the United States – was viewed as an invaluable weapon in the Cold War.
A Three-Year Climatology of Cloud-Top Phase over the Southern Ocean and North Pacific
Authors: Morrison Anthony E. , Siems Steven T. , Manton Michael J. 
Published: January 2011

Abstract
Moderate Resolution Imaging Spectroradiometer (MODIS) Level 2 observations from the Terra satellite are used to create a 3-yr climatology of cloud-top phase over a section of the Southern Ocean (south of Australia) and the North Pacific Ocean. The intent is to highlight the extensive presence of supercooled liquid water over the Southern Ocean region, particularly during summer. The phase of such clouds directly affects the absorbed shortwave radiation, which has recently been found to be “poorly simulated in both state-of-the-art reanalysis and coupled global climate models” (Trenberth and Fasullo).
The climatology finds that supercooled liquid water is present year-round in the low-altitude clouds across this section of the Southern Ocean. Further, the MODIS cloud phase algorithm identifies very few glaciated cloud tops at temperatures above −20°C, rather inferring a large portion of “uncertain” cloud tops. Between 50° and 60°S during the summer, the albedo effect is compounded by a seasonal reduction in high-level cirrus. This is in direct contrast to the Bering Sea and Gulf of Alaska. Here MODIS finds a higher likelihood of observing warm liquid water clouds during summer and a reduction in the relative frequency of cloud tops within the 0° to −20°C temperature range.
As the MODIS cloud phase product has limited ability to confidently identify cloud-top phase between −5° and −25°C, future research should include observations from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and other space-based sensors to help with the classification within this temperature range. Further, multiregion in situ verification of any remotely sensed observations is vital to further understanding the cloud phase processes.
The Role of Nonlinear Momentum Fluxes on the Evolution of Directional Wind-Wave Spectra
Authors: Resio Donald T. , Long Charles E. , Perrie William 
Published: January 2011

Abstract
It has long been known that nonlinear wave–wave interactions produce stationary solutions related to constant energy flux through the equilibrium range when a deep-water spectrum follows an f−4 form, as has been verified in numerical studies in which spectra follow a constant angular spreading distribution. This paper shows that, although energy fluxes through such spectra remain essentially constant, momentum fluxes do not. On the other hand, if the angular distribution of a spectrum is allowed to behave in a manner consistent with observations, both the energy flux and the momentum flux tend to remain constant through a major portion of the spectrum. Thus, it appears that directional distributions of energy within wind-wave spectra adjust to a form consistent with nondivergent nonlinear fluxes, suggesting that these fluxes likely play a very prominent role in the evolution of directional spectra during wave generation.
Automated Lightning Flash Detection in Nighttime Visible Satellite Data
Authors: Bankert Richard L. , Solbrig Jeremy E. , Lee Thomas F. , Miller Steven D. 
Published: January 2011

Abstract
The Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS) nighttime visible channel was designed to detect earth–atmosphere features under conditions of low illumination (e.g., near the solar terminator or via moonlight reflection). However, this sensor also detects visible light emissions from various terrestrial sources (both natural and anthropogenic), including lightning-illuminated thunderstorm tops. This research presents an automated technique for objectively identifying and enhancing the bright steaks associated with lightning flashes, even in the presence of lunar illumination, derived from OLS imagery. A line-directional filter is applied to the data in order to identify lightning strike features and an associated false color imagery product enhances this information while minimizing false alarms. Comparisons of this satellite product to U.S. National Lightning Detection Network (NLDN) data in one case as well as to a lightning mapping array (LMA) in another case demonstrate general consistency to within the expected limits of detection. This algorithm is potentially useful in either finding or confirming electrically active storms anywhere on the globe, particularly those occurring in remote areas where surface-based observations are not available. Additionally, the OLS nighttime visible sensor provides heritage data for examining the potential usefulness of the Visible-Infrared Imager-Radiometer Suite (VIIRS) Day/Night Band (DNB) on future satellites including the National Polar-orbiting Operational Environmental Satellite System (NPOESS) Preparatory Project (NPP). The VIIRS DNB will offer several improvements to the legacy OLS nighttime visible channel, including full calibration and collocation with 21 narrowband spectral channels.
Association Rule Data Mining Applications for Atlantic Tropical Cyclone Intensity Changes
Authors: Yang Ruixin , Tang Jiang , Sun Donglian 
Published: January 2011

Abstract
This study applies a data mining technique called association rule mining to the analysis of intensity changes of North Atlantic tropical cyclones (TCs). The “best track” data from the National Hurricane Center and the Statistical Hurricane Intensity Prediction Scheme databases were stratified into tropical depressions, tropical storms, and category 1–5 hurricanes based on the Saffir–Simpson hurricane scale. After stratification, the seven resulting groups of TCs plus two additional aggregation groups were further separated into intensifying, weakening, and stable TCs. The analysis of the stratified data for preprocessing revealed that faster northward storm motion (the meridional component of storm motion) favors tropical storm intensification but does not favor the intensification of hurricanes. Intensifying tropical storms are more strongly associated with a higher convergence in the upper atmosphere (200-hPa relative eddy momentum flux convergence) than weakening tropical storms, while intensifying hurricanes are more strongly associated with lower convergence values. The mined association rules showed that cofactors usually display higher-intensity prediction power in the stratified TC groups. The data mining results also identified a predictor set with fewer factors but improved probabilities of rapid intensification. This study found that the data mining technique not only sheds light on the roles of multiple-associated physical processes in tropical cyclone development—especially in rapid intensification processes—but also will help improve TC intensity forecasting. This paper provides an outline on how to use this data mining technique and how to overcome low occurrences of mined conditions in order to improve TC intensity forecasting capabilities.