bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporation of Eukaryotic Translation Initiation Factor eIF4E into Viral Nucleocapsids via Interaction with Hepatitis B Virus Polymerase
Authors: Kim Seahee , Wang Haifeng , Ryu Wang-Shick 
Published: September 2009

ABSTRACT

The DNA genome of hepatitis B virus (HBV) replicates via reverse transcription within capsids following the encapsidation of an RNA template, the pregenomic RNA (pgRNA). We previously demonstrated that the 5′ cap proximity of the stem-loop structure (ε or epsilon), an encapsidation signal, is critically important for the encapsidation of the pgRNA (J. K. Jeong, G. S. Yoon, and W. S. Ryu, J. Virol.
74:
5502-5508, 2000). Therefore, we speculated that the viral polymerase (Pol), while bound to the 5′ ε stem-loop structure, could recognize the cap via its interaction with eIF4E, a eukaryotic translation initiation factor. Our data showed the direct interaction between HBV Pol and eIF4E, as measured by coimmunoprecipitation. Further, we demonstrated that eIF4E interacts with the Pol-ε ribonucleoprotein complex (RNP) rather than Pol alone, resulting in eIF4E-Pol-ε RNP complex formation. In addition, we asked whether eIF4E remains engaged to the Pol-ε RNP complex during nucleocapsid assembly. Density gradient analysis revealed that eIF4E indeed was incorporated into nucleocapsids. It is of great importance to uncover whether the incorporated eIF4E contributes to viral reverse transcription or other steps in the HBV life cycle.
Bacteriophage-Mediated Toxin Gene Regulation in
Clostridium difficile
Authors: Govind Revathi , Vediyappan Govindsamy , Rolfe Rial D. , Dupuy Bruno , Fralick Joe A. 
Published: September 2009

ABSTRACT

Clostridium difficile
has been identified as the most important single identifiable cause of nosocomial antibiotic-associated diarrhea and colitis. Virulent strains of
C. difficile
produce two large protein toxins, toxin A and toxin B, which are involved in pathogenesis. In this study, we examined the effect of lysogeny by ΦCD119 on
C. difficile
toxin production. Transcriptional analysis demonstrated a decrease in the expression of pathogenicity locus (PaLoc) genes
tcdA
,
tcdB
,
tcdR
,
tcdE
, and
tcdC
in ΦCD119 lysogens. During this study we found that
repR
, a putative repressor gene of ΦCD119, was expressed in
C. difficile
lysogens and that its product, RepR, could downregulate
tcdA
::
gusA
and
tcdR
::
gusA
reporter fusions in
Escherichia coli
. We cloned and purified a recombinant RepR containing a C-terminal six-His tag and documented its binding to the upstream regions of
tcdR
in
C. difficile
PaLoc and in
repR
upstream region in ΦCD119 by gel shift assays. DNA footprinting experiments revealed similarities between the RepR binding sites in
tcdR
and
repR
upstream regions. These findings suggest that presence of a CD119-like temperate phage can influence toxin gene regulation in this nosocomially important pathogen.
Structure-Function Analysis of Human Immunodeficiency Virus Type 1 gp120 Amino Acid Mutations Associated with Resistance to the CCR5 Coreceptor Antagonist Vicriviroc
Authors: Ogert Robert A. , Ba Lei , Hou Yan , Buontempo Catherine , Qiu Ping , Duca Jose , Murgolo Nicholas , Buontempo Peter , Ralston Robert , Howe John A. 
Published: September 2009

ABSTRACT

Vicriviroc (VCV) is a small-molecule CCR5 coreceptor antagonist currently in clinical trials for treatment of R5-tropic human immunodeficiency virus type 1 (HIV-1) infection. With this drug in development, identification of resistance mechanisms to VCV is needed to allow optimal outcomes in clinical practice. In this study we further characterized VCV resistance in a lab-adapted, VCV-resistant RU570 virus (RU570-VCV
res
). We show that K305R, R315Q, and K319T amino acid changes in the V3 loop, along with P437S in C4, completely reproduced the resistance phenotype in a chimeric ADA envelope containing the C2-V5 region from RU570 passage control gp120. The K305R amino acid change primarily impacted the degree of resistance, whereas K319T contributed to both resistance and virus infectivity. The P437S mutation in C4 had more influence on the relative degree of virus infectivity, while the R315Q mutation contributed to the virus concentration-dependent phenotypic resistance pattern observed for RU570-VCV
res
. RU570-VCV
res
pseudovirus entry with VCV-bound CCR5 was dramatically reduced by Y10A, D11A, Y14A, and Y15A mutations in the N terminus of CCR5, whereas these mutations had less impact on entry in the absence of VCV. Notably, an additional Q315E/I317F substitution in the crown region of the V3 loop enhanced resistance to VCV, resulting in a stronger dependence on the N terminus for viral entry. By fitting the envelope mutations to a molecular model of a recently described docked N-terminal CCR5 peptide consisting of residues 2 to 15 in complex with HIV-1 gp120 CD4, potential new interactions in gp120 with the N terminus of CCR5 were uncovered. The cumulative results of this study suggest that as the RU570 VCV-resistant virus adapted to use the drug-bound receptor, it also developed an increased reliance on the N terminus of CCR5.
Functional Analysis and Structural Modeling of Human APOBEC3G Reveal the Role of Evolutionarily Conserved Elements in the Inhibition of Human Immunodeficiency Virus Type 1 Infection and
Alu
Transposition
Authors: Bulliard Yannick , Turelli Priscilla , Röhrig Ute F. , Zoete Vincent , Mangeat Bastien , Michielin Olivier , Trono Didier 
Published: September 2009

ABSTRACT

Retroelements are important evolutionary forces but can be deleterious if left uncontrolled. Members of the human APOBEC3 family of cytidine deaminases can inhibit a wide range of endogenous, as well as exogenous, retroelements. These enzymes are structurally organized in one or two domains comprising a zinc-coordinating motif. APOBEC3G contains two such domains, only the C terminal of which is endowed with editing activity, while its N-terminal counterpart binds RNA, promotes homo-oligomerization, and is necessary for packaging into human immunodeficiency virus type 1 (HIV-1) virions. Here, we performed a large-scale mutagenesis-based analysis of the APOBEC3G N terminus, testing mutants for (i) inhibition of
vif
-defective HIV-1 infection and
Alu
retrotransposition, (ii) RNA binding, and (iii) oligomerization. Furthermore, in the absence of structural information on this domain, we used homology modeling to examine the positions of functionally important residues and of residues found to be under positive selection by phylogenetic analyses of primate APOBEC3G genes. Our results reveal the importance of a predicted RNA binding dimerization interface both for packaging into HIV-1 virions and inhibition of both HIV-1 infection and
Alu
transposition. We further found that the HIV-1-blocking activity of APOBEC3G N-terminal mutants defective for packaging can be almost entirely rescued if their virion incorporation is forced by fusion with Vpr, indicating that the corresponding region of APOBEC3G plays little role in other aspects of its action against this pathogen. Interestingly, residues forming the APOBEC3G dimer interface are highly conserved, contrasting with the rapid evolution of two neighboring surface-exposed amino acid patches, one targeted by the Vif protein of primate lentiviruses and the other of yet-undefined function.
Identification and Mutational Analysis of a Rej Response Element in Jaagsiekte Sheep Retrovirus RNA
Authors: Nitta Takayuki , Hofacre Andrew , Hull Stacey , Fan Hung 
Published: September 2009

ABSTRACT

Jaagsiekte sheep retrovirus (JSRV) is a simple betaretrovirus causing a contagious lung cancer of sheep. JSRV encodes unspliced and spliced viral RNAs, among which unspliced RNA encodes Gag and Pol proteins and a singly spliced mRNA encodes Env protein. In another study we found that JSRV encodes a regulatory protein, Rej, that is responsible for synthesis of Gag polyprotein from unspliced viral RNA. Rej is encoded in the 5′ end of
env
, and it enhances nuclear export or accumulation of cytoplasmic unspliced viral RNA in 293T cells but not in most other cell lines (A. Hofacre, T. Nitta, and H. Fan, J. Virol. 83:12483-12498, 2009). In this study, we found that mutations in the 3′ end of
env
in the context of a cytomegalovirus-driven full-length JSRV expression construct abolished Gag protein synthesis and released viruses in 293T cells. These mutants also showed deficits in accumulation of unspliced viral RNA in the cytoplasm. These mutants defined a Rej-responsive element (RejRE). Inhibition of CRM1 but not Tap function prevented nuclear export/accumulation of cytoplasmic unspliced RNA in 293T cells, similarly to other complex retroviruses that express analogous regulator proteins (e.g., human immunodeficiency virus Rev). Structural modeling of the RejRE with Zuker M-fold indicated a region with a predicted stable secondary structure. Mutational analysis in this region indicated the importance of both secondary structures and primary nucleotide sequences in a central stem-bulge-stem structure. In contrast to 293T cells, mutations in the RejRE did not affect the levels of cytoplasmic unspliced RNA in 293 cells, although the unspliced RNA showed partial degradation, perhaps due to lack of translation. RejRE-containing RNA relocalized Rej protein from the nucleus to the cytoplasm in 293 and rat 208F cells, suggesting binding of Rej to the RejRE.
A 1–10-Day Ensemble Forecasting Scheme for the Major River Basins of Bangladesh: Forecasting Severe Floods of 2003–07*
Authors: Hopson Thomas M. , Webster Peter J. 
Published: September 2009

Abstract
This paper describes a fully automated scheme that has provided calibrated 1–10-day ensemble river discharge forecasts and predictions of severe flooding of the Brahmaputra and Ganges Rivers as they flow into Bangladesh; it has been operational since 2003. The Bangladesh forecasting problem poses unique challenges because of the frequent life-threatening flooding of the country and because of the absence of upstream flow data from India means that the Ganges and Brahmaputra basins must be treated as if they are ungauged. The meteorological–hydrological forecast model is a hydrologic multimodel initialized by NASA and NOAA precipitation products, whose states and fluxes are forecasted forward using calibrated European Centre for Medium-Range Weather Forecasts ensemble prediction system products, and conditionally postprocessed to produce calibrated probabilistic forecasts of river discharge at the entrance points of the Ganges and Brahmaputra into Bangladesh. Forecasts with 1–10-day horizons are presented for the summers of 2003–07. Objective verification shows that the forecast system significantly outperforms both a climatological and persistence forecast at all lead times. All severe flooding events were operationally forecast with significant probability at the 10-day horizon, including the extensive flooding of the Brahmaputra in 2004 and 2007, with the latter providing advanced lead-time warnings for the evacuation of vulnerable residents.
Interference Pattern and Propagation of the M2 Internal Tide South of the Hawaiian Ridge
Authors: Rainville Luc , Johnston T. M. Shaun , Carter Glenn S. , Merrifield Mark A. , Pinkel Robert , Worcester Peter F. , Dushaw Brian D. 
Published: September 2009

Abstract
Most of the M2 internal tide energy generated at the Hawaiian Ridge radiates away in modes 1 and 2, but direct observation of these propagating waves is complicated by the complexity of the bathymetry at the generation region and by the presence of interference patterns. Observations from satellite altimetry, a tomographic array, and the R/P FLIP taken during the Farfield Program of the Hawaiian Ocean Mixing Experiment (HOME) are found to be in good agreement with the output of a high-resolution primitive equation model, simulating the generation and propagation of internal tides. The model shows that different modes are generated with different amplitudes along complex topography. Multiple sources produce internal tides that sum constructively and destructively as they propagate. The major generation sites can be identified using a simplified 2D idealized knife-edge ridge model. Four line sources located on the Hawaiian Ridge reproduce the interference pattern of sea surface height and energy flux density fields from the numerical model for modes 1 and 2. Waves from multiple sources and their interference pattern have to be taken into account to correctly interpret in situ observations and satellite altimetry.
Impact of Phased-Array Radar Observations over a Short Assimilation Period: Observing System Simulation Experiments Using an Ensemble Kalman Filter
Authors: Yussouf Nusrat , Stensrud David J. 
Published: September 2009

Abstract
The conventional Weather Surveillance Radar-1988 Doppler (WSR-88D) scans a given weather phenomenon in approximately 5 min, and past results suggest that it takes 30–60 min to establish a storm into a model assimilating these data using an ensemble Kalman filter (EnKF) data assimilation technique. Severe-weather events, however, can develop and evolve very rapidly. Therefore, assimilating observations for a 30–60-min period prior to the availability of accurate analyses may not be feasible in an operational setting. A shorter assimilation period also is desired if forecasts are produced to increase the warning lead time. With the advent of the emerging phased-array radar (PAR) technology, it is now possible to scan the same weather phenomenon in less than 1 min. Therefore, it is of interest to see if the faster scanning rate of PAR can yield improvements in storm-scale analyses and forecasts from assimilating over a shorter period of time. Observing system simulation experiments are conducted to evaluate the ability to quickly initialize a storm into a numerical model using PAR data in place of WSR-88D data. Synthetic PAR and WSR-88D observations of a splitting supercell storm are created from a storm-scale model run using a realistic volume-averaging technique in native radar coordinates. These synthetic reflectivity and radial velocity observations are assimilated into the same storm-scale model over a 15-min period using an EnKF data assimilation technique followed by a 50-min ensemble forecast. Results indicate that assimilating PAR observations at 1-min intervals over a short 15-min period yields significantly better analyses and ensemble forecasts than those produced using WSR-88D observations. Additional experiments are conducted in which the adaptive scanning capability of PAR is utilized for thunderstorms that are either very close to or far away from the radar location. Results show that the adaptive scanning capability improves the analyses and forecasts when compared with the nonadaptive PAR data. These results highlight the potential for flexible rapid-scanning PAR observations to help to quickly and accurately initialize storms into numerical models yielding improved storm-scale analyses and very short range forecasts.
On the Predictability of Mesoscale Convective Systems: Three-Dimensional Simulations
Authors: Wandishin Matthew S. , Stensrud David J. , Mullen Steven L. , Wicker Louis J. 
Published: September 2009

Abstract
Mesoscale convective systems (MCSs) are a dominant climatological feature of the central United States and are responsible for a substantial fraction of warm-season rainfall. Yet very little is known about the predictability of MCSs. To help address this situation, a previous paper by the authors examined a series of ensemble MCS simulations using a two-dimensional version of a storm-scale (Δx = 1 km) model. Ensemble member perturbations in the preconvective environment, namely, wind speed, relative humidity, and convective instability, are based on current 24-h forecast errors from the North American Model (NAM). That work is now extended using a full three-dimensional model.
Results from the three-dimensional simulations of the present study resemble those found in two dimensions. The model successfully produces an MCS within 100 km of the location of the control run in around 70% of the ensemble runs using perturbations to the preconvective environment consistent with 24-h forecast errors, while reducing the preconvective environment uncertainty to the level of current analysis errors improves the success rate to nearly 85%. This magnitude of improvement in forecasts of environmental conditions would represent a radical advance in numerical weather prediction. The maximum updraft and surface wind forecast uncertainties are of similar magnitude to their two-dimensional counterparts. However, unlike the two-dimensional simulations, in three dimensions, the improvement in the forecast uncertainty of storm features requires the reduction of preconvective environmental uncertainty for all perturbed variables. The MCSs in many of the runs resemble bow echoes, but surface winds associated with these solutions, and the perturbation profiles that produce them, are nearly indistinguishable from the nonbowing solutions, making any conclusions about the bowlike systems difficult.
Clinical and Radiologic Outcomes of Arthroscopic Glenoid Labrum Repair With the BioKnotless Suture Anchor
Authors: Oh Joo Han , Lee Ho Kyoo , Kim Jae Yoon , Kim Sae Hoon , Gong Hyun Sik 
Published: September 2009

Background Although arthroscopic glenoid labrum repair using the BioKnotless anchor is common, the benefits and efficacy have not been fully evaluated. Hypothesis BioKnotless suture anchor is a clinically and radiologically suitable material for arthroscopic labral repair. Study Design Case series; Level of evidence, 4. Methods Ninety-seven patients underwent arthroscopic glenoid labrum repair with BioKnotless anchor between July 2004 and December 2005. Thirty-seven patients had traumatic anterior instability and 60 patients had an isolated superior labrum, anterior-posterior (SLAP) lesion. The mean age at surgery was 36.0 years (range, 15–66); the average follow-up was 34.1 months (range, 24–54). Clinical outcomes were evaluated using range of motion and various functional evaluation scores including sports activity. Pain and patient satisfaction were measured using a visual analog scale (VAS). Computed tomography arthrography was conducted in 73 patients at least 1 year after surgery for radiologic evaluation. Results In patients with instability, the Western Ontario Shoulder Instability index and Rowe score improved from 53.2 to 85.9 and from 68.7 to 92.7, respectively. Return to normal recreation and sports were possible in 30 patients (81.1%); the mean satisfaction VAS was 9.2. There was 1 postoperative dislocation, and the apprehension test was positive in 1 case. Postoperative range of motion including external rotation was not different. In patients with a SLAP lesion, the American Shoulder and Elbow Surgeons score and Constant score improved from 67.3 to 96.0 and 79.1 to 96.8, respectively. Pain VAS decreased from 6.0 to 0.4, and the mean satisfaction VAS was 9.4. Return to normal recreation and sports were possible in 50 patients (83.3%). All labra were found to have firmly healed to bony glenoid rim without anchor-related osteolysis in postoperative CT arthrography. Conclusion Clinically and radiologically, the BioKnotless anchor appears to be an acceptable alternative for arthroscopic labrum repair, and a suitable material allowing the avoidance of certain troublesome drawbacks of the conventional knot-tying suture anchor.
Some Political Meanings of ‘Civilization’
Authors: Kapustin Boris 
Published: September 2009

AbstractSince the early nineties, the term ‘civilization’ has undergone remarkable transformations and has assumed political and ideological functions it has not been fit for as a linchpin of the more than two-centuries-old academic discourse on ‘civilizations’. These transformations materialized in the political-ideological formations known as the ‘clash of civilizations’ and the ‘dialogue among civilizations’ which comprise a ‘civilizational discourse’ in many respects alternative to the academic one. This essay intends, firstly, to uncover the structural and thematic differences between the academic ‘civilizational discourse’ and its trendy alternative. Secondly, the essay aspires to demonstrate how complementary, at their methodological and ideological bases, the ‘clash of civilizations’ and the ‘dialogue among civilizations’ are, despite their highly-publicized antagonism. Thirdly, the article aims to highlight the actual political processes underway in our world which manifest themselves through and make use of the alternative ‘civilizational discourse’ as part of their modus operandi. The essay ties these processes with the global triumph of capitalism at the closure of the 20th century, and with the rise of the projects of authoritarian hegemony.
Remarks on Russian Philosophy, Soviet Philosophy, and Historicism
Authors: Rockmore Tom 
Published: September 2009

AbstractThis paper concerns two themes: my personal experience of Russian philosophy and Russian philosophers on the one hand, and historicism on the other. My account of my limited experience of Russian philosophers and philosophy will be mainly autobiographical. My remarks about historicism will concern a single aspect of the philosophical consequences of the Soviet experience for Russian philosophy. When I come to Russia, I am always surprised by the degree of interest in a historical approach to knowledge, an interest that, so far as I know, is unique to Russian philosophy. This difference in perspective as concerns the historical character of cognitive claims needs to be explained. It needs to be explained why contemporary Russian philosophers and contemporary Russian philosophy are so hospitable to a historical approach to knowledge, an approach which has always been rare, even unusual, elsewhere. My hypothesis, which I examine the paper, is that there is a deep link between contemporary Russian interest in a historical approach to knowledge and Soviet philosophy. In particular, there is a link to Marx, who is a historical thinker, and to pre-Soviet Russian philosophy, as distinguished from Marxism, which is basically a-historical.
The Place of Russian Philosophy in World Philosophical History — A Perspective
Authors: van der Zweerde Evert 
Published: September 2009

AbstractThis paper sketches the ambitious outlines of an assessment of the place of Russian philosophy in philosophical history ‘at large’, i.e. on a global and world-historical scale. At the same time, it indicates, rather modestly, a number of elements and aspects of such a project. A retrospective reflection and reconstruction is not only a recurrent phenomenon in philosophical culture (which, the author assumes, has become global), it also is, by virtue of its being a philosophical reflection, one among many possible perspectives. The central claim of the paper is that the key to an assessment of the world-historical place of Russian philosophy is to be found in the Soviet period, not only because it was, through its isolation policy and its subordination of philosophy to political and ideological goals, a determining factor for a large part of the 20th century, but also, and more importantly, because it has systematically distorted the perception of Russia's philosophical history, including of the Soviet episode itself. The very undoing of these distortions, however, risks becoming a distortion because of, on the one hand, a demonization of the Soviet factor and, on the other hand, a disregard for its philosophical and meta-philosophical relevance.