bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Single Amino Acid Substitution in HIV-1 Reverse Transcriptase Significantly Reduces Virion Release
Authors: Chiang Chien-Cheng , Wang Shiu-Mei , Pan Yen-Yu , Huang Kuo-Jung , Wang Chin-Tien 
Published: November 2009

ABSTRACT
HIV-1 protease (PR) mediates the proteolytic processing of virus particles during or after virus budding. PR activation is thought to be triggered by appropriate Gag-Pol/Gag-Pol interaction; factors affecting this interaction either enhance or reduce PR-mediated cleavage efficiency, resulting in markedly reduced virion production or the release of inadequately processed virions. We previously showed that a Gag-Pol deletion mutation involving the reverse transcriptase tryptophan (Trp) repeat motif markedly impairs PR-mediated virus maturation and that an alanine substitution at W401 (W401A) or at both W401 and W402 (W401A/W402A) partially or almost completely negates the enhancement effect of efavirenz (a nonnucleoside reverse transcriptase inhibitor) on PR-mediated virus processing efficiency. These data suggest that the Trp repeat motif may contribute to the PR activation process. Here we demonstrate that due to enhanced Gag cleavage efficiency, W402 alanine or leucine substitution significantly reduces virus production. However, W402 replacement with phenylalanine does not significantly affect virus particle assembly or processing, but it does markedly impair viral infectivity in a single-cycle infection assay. Our results demonstrate that a single amino acid substitution at HIV-1 RT can radically affect virus assembly by enhancing Gag cleavage efficiency, suggesting that in addition to contributing to RT biological function during the early stages of virus replication, the HIV-1 RT tryptophan repeat motif in a Gag-Pol context may play an important role in suppressing the premature activation of PR during late-stage virus replication.
Evolutionary Patterns of Eastern Equine Encephalitis Virus in North versus South America Suggest Ecological Differences and Taxonomic Revision
Authors: Arrigo Nicole C. , Adams A. Paige , Weaver Scott C. 
Published: November 2009

ABSTRACTThe eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories. The structural polyprotein open reading frames of all available SA EEEV and recent NA EEEV isolates were sequenced and used in evolutionary and phylogenetic analyses. The nucleotide substitution rate per year for SA EEEV (1.2 × 10−4) was lower and more consistent than that for NA EEEV (2.7 × 10−4), which exhibited considerable rate variation among constituent clades. Estimates of time since divergence varied widely depending upon the sequences used, with NA and SA EEEV diverging ca. 922 to 4,856 years ago and the two main SA EEEV lineages diverging ca. 577 to 2,927 years ago. The single, monophyletic NA EEEV lineage exhibited mainly temporally associated relationships and was highly conserved throughout its geographic range. In contrast, SA EEEV comprised three divergent lineages, two consisting of highly conserved geographic groupings that completely lacked temporal associations. A phylogenetic comparison of SA EEEV and Venezuelan equine encephalitis viruses (VEEV) demonstrated similar genetic and evolutionary patterns, consistent with the well-documented use of mammalian reservoir hosts by VEEV. Our results emphasize the evolutionary and genetic divergences between members of the NA and SA EEEV lineages, consistent with major differences in pathogenicity and ecology, and propose that NA and SA EEEV be reclassified as distinct species in the EEE complex.
The Open Reading Frame 3a Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Promotes Membrane Rearrangement and Cell Death
Authors: Freundt Eric C. , Yu Li , Goldsmith Cynthia S. , Welsh Sarah , Cheng Aaron , Yount Boyd , Liu Wei , Frieman Matthew B. , Buchholz Ursula J. , Screaton Gavin R. , Lippincott-Schwartz Jennifer , Zaki Sherif R. , Xu Xiao-Ning , Baric Ralph S. , Subbarao Kanta , Lenardo Michael J. 
Published: November 2009

ABSTRACT
The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.
Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology
Authors: Murawski Matthew R. , McGinnes Lori W. , Finberg Robert W. , Kurt-Jones Evelyn A. , Massare Michael J. , Smith Gale , Heaton Penny M. , Fraire Armando E. , Morrison Trudy G. 
Published: November 2009

ABSTRACT
Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 μg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G-immunized mice, no enhanced pathology in the lungs was observed, although lungs of mice immunized in parallel with formalin-inactivated RSV (FI-RSV) showed the significant pathology that has previously been documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs, with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for protection against RSV.
Analysis of the Viral Elements Required in the Nuclear Import of HIV-1 DNA
Authors: Rivière Lise , Darlix Jean-Luc , Cimarelli Andrea 
Published: November 2009

ABSTRACT

HIV-1 possesses an exquisite ability to infect cells independently from their cycling status by undergoing an active phase of nuclear import through the nuclear pore. This property has been ascribed to the presence of karyophilic elements present in viral nucleoprotein complexes, such as the matrix protein (MA); Vpr; the integrase (IN); and a
cis
-acting structure present in the newly synthesized DNA, the DNA flap. However, their role in nuclear import remains controversial at best. In the present study, we carried out a comprehensive analysis of the role of these elements in nuclear import in a comparison between several primary cell types, including stimulated lymphocytes, macrophages, and dendritic cells. We show that despite the fact that none of these elements is absolutely required for nuclear import, disruption of the central polypurine tract-central termination sequence (cPPT-CTS) clearly affects the kinetics of viral DNA entry into the nucleus. This effect is independent of the cell cycle status of the target cells and is observed in cycling as well as in nondividing primary cells, suggesting that nuclear import of viral DNA may occur similarly under both conditions. Nonetheless, this study indicates that other components are utilized along with the cPPT-CTS for an efficient entry of viral DNA into the nucleus.
Epstein-Barr Viruses That Express a CD21 Antibody Provide Evidence that gp350's Functions Extend beyond B-Cell Surface Binding
Authors: Busse Clemens , Feederle Regina , Schnölzer Martina , Behrends Uta , Mautner Josef , Delecluse Henri-Jacques 
Published: November 2009

ABSTRACTThe gp350 glycoprotein encoded by BLLF1 is crucial for efficient Epstein-Barr virus (EBV) infection of resting B cells. Gp350 binds to CD21, but whether this interaction sums up its functions remains unknown. We generated gp350-null EBVs that display CD19-, CD21-, or CD22-specific antibodies at their surface (designated as ΔBLLF1-Ab). Gp350-complemented (ΔBLLF1-C) and ΔBLLF1-Ab were found to bind equally well to B cells. Surprisingly, ΔBLLF1 binding was reduced only 1.7-fold relative to its complemented counterparts. Furthermore, B cells exposed to ΔBLLF1-Ab or ΔBLLF1 viruses presented structural antigens with comparable efficiency and achieved 25 to 80% of the T-cell activation elicited by ΔBLLF1-C. These findings show that the gp350-CD21 interaction pair plays only a modest role during virus transfer to the endosomal compartment. However, primary B cells or Raji B cells infected with ΔBLLF1-C viruses displayed a 35- to 70-fold higher infection rates than those exposed to ΔBLLF1, ΔBLLF1-CD22Ab, or ΔBLLF1-CD19Ab viruses. Complementation of the gp350 knockout phenotype with CD21Ab substantially enhanced infection rates relative to ΔBLLF1 but remained sevenfold (Raji B-cell line) to sixfold (primary B cells) less efficient than with gp350. We therefore infer that gp350 mainly exerts its functions after the internalization step, presumably during release of the viral capsid from the endosomal compartment, and that CD21-dependent but also CD21-independent molecular mechanisms are involved in this process. The latter appear to be characteristic of B-cell infection since transfection of CD21 in 293 cells improved the infection rates with both ΔBLLF1-CD21Ab and ΔBLLF1-C to a similar extent.
Musculoskeletal pain at multiple sites and its effects on work ability in a general working population
Authors: Miranda Helena , Kaila-Kangas Leena , Heliövaara Markku , Leino-Arjas Päivi , Haukka Eija , Liira Juha , Viikari-Juntura Eira 
Published: November 2009

ObjectivesMusculoskeletal pain often occurs at multiple sites concurrently. The aim of this study was to examine the associations between multi-site pain and self-rated work ability and retirement plans among actively working people.MethodsThe Health 2000 Survey was carried among a representative sample of Finnish adults. Musculoskeletal pain during the preceding month in the lower back, neck or shoulders, upper extremities, hips and lower extremities, and work ability and intentions to retire early were assessed. Subjects were also clinically examined. Analyses were restricted to 30–64-year-old subjects actively working during the preceding 12 months who provided information on work ability outcomes (population-weighted number of subjects=4087). Log-binomial regression was used to estimate prevalence ratios of reduced work ability.ResultsSingle-site pain was reported by 33% of subjects, 20%, 9% and 4% reported pain in two, three and four sites, respectively, and 8%–15% reported poor work ability. Every fifth person had thought about retiring early. Age- and gender-adjusted risks of poor physical work ability and own prognosis of poor future work ability increased from 2 for single-site pain to 8 for pain at four sites. Risks remained considerably elevated after adjustment for various covariates, including clinical musculoskeletal disorders and functional capacity. Poor current work ability was most affected by multi-site pain at older age (50–64 years) and intentions to retire early at age 40–49 years.ConclusionsCo-occurring pain is a considerable threat to work ability. Workers with multi-site pain may benefit from targeted preventive measures to sustain their work ability. Future studies should also consider multi-site pain as an important risk factor for reduced work ability.
Multimodality imaging in hyperparathyroidism
Authors: Patel C N , Scarsbrook A F 
Published: November 2009

Abstract
Imaging of patients with hyperparathyroidism has evolved over the last decade and transformed surgical management of the disease. Traditional bilateral neck dissection and exploratory surgery has been overtaken by focused, minimally invasive procedures in patients with single-gland disease. Accurate preoperative localisation of the involved parathyroid gland is the cornerstone for success of the new surgical techniques. In this article, the strengths, limitations and respective roles of different imaging modalities used to evaluate patients with hyperparathyroidism will be reviewed.
A doctor’s experience of resuscitation decision making for older patients: coping with change
Authors: Bowker L 
Published: November 2009

Abstract
There has been a dramatic change in the way that resuscitation decisions are made for older hospital inpatients in the UK. In less than 20 years many geriatric medicine wards have moved from an “opt-in” policy (where the default position is not to provide resuscitation) to a position where resuscitation is widely available to older patients and clinicians are much more reluctant to make “do not attempt cardiopulmonary resuscitation” decisions on medical grounds alone. The drivers for this change are rooted in societal changes rather than scientific or legal advances. Older patients are increasingly educated and have higher expectations of health care, while doctors are more commonly criticised and have progressively less “power” in the doctor–patient relationship. Doctors in the UK are struggling with the growing volume and complexity of guidelines about resuscitation, which can prove very tricky to enact within current resources and priorities. Many are feeling stressed and under equipped to cope with the ethical and legal dilemmas of resuscitation decision making. The solution lies in better undergraduate and postgraduate training which enhances skills (such as consultation skills and ethical reasoning) and not just knowledge of laws, principles and guidelines.
Conference Report: Seventh Annual AACR International Conference on Frontiers in Cancer Prevention Research
Authors: Brown Powel H. , Viner Jaye L. , Brewster Abenaa , Heckman Carolyn J. , Hursting Stephen , Johnson Karen , Mao Jenny T. 
Published: November 2009

Abstract
In November, 2008 the AACR held the Seventh Annual Frontiers in Cancer Prevention Research meeting in Washington, DC. At this meeting, a wide range of cutting-edge cancer prevention research was presented. This summary highlights some of the most impactful presentations with a focus on the interaction between inflammation, infections, the immune system, and tumor microenvironment in promoting cancer. Several of these presentations described targeting host-tumor interactions as a means for cancer prevention. As discussed below, this meeting continues to represent all phases of cancer prevention research including epidemiologic studies, behavioral and lifestyle interventions, carcinogenesis research, preclinical studies testing novel preventive interventions, and the results of early- and late-phase cancer prevention trials. Major advances presented at the 2008 meeting included studies showing that immune cells can be either protumorigenic or antitumorigenic, efforts to develop more comprehensive human papillomavirus vaccines to more effectively prevent cervical cancer and other human papillomavirus–related cancers, controversial studies of vitamin D and cancer risk, and studies of single-nucleotide polymorphisms to better assess cancer risk. These and the other presentations at this meeting continue to provide strong support for the concept that cancer will be most effectively controlled by applying modern cancer prevention strategies
Haggai and Ezekiel: The Complicated Relations between the Two Prophets
Authors: Kasher Rimon 
Published: November 2009

AbstractThe issue of a possible link between Haggai and Ezekiel (the prophets and the books) was raised in the recent years by several scholars. Among them are P. D. Hanson (1975), C. Stuhlmueller (1988), A. Laato (1992), and S. S. Tuell (2003). In this article we will examine some of the main arguments. It is our conclusion, based on a careful examination of the arguments, that only a few are valid. Yet we can show that both Haggai and Ezekiel share some prominent components of their world views. Both seem to belong to a millennial movement (based on a anthropological definition); both based their concepts upon theocentricity, and both deal seriously with the question of God's status. Their solutions are however quite different, due to their own experience and the difference in political and social situations.
Validation of Precipitable Water Vapor within the NCEP/DOE Reanalysis Using Global GPS Observations from One Decade
Authors: Vey Sibylle , Dietrich Reinhard , Rülke Axel , Fritsche Mathias , Steigenberger Peter , Rothacher Markus 
Published: November 2009

AbstractIn contrast to previous studies validating numerical weather prediction (NWP) models using observations from the global positioning system (GPS), this paper focuses on the validation of seasonal and interannual variations in the water vapor. The main advantage of the performed validation is the independence of the GPS water vapor estimates compared to studies using water vapor datasets from radiosondes or satellite microwave radiometers that are already assimilated into the NWP models. Tropospheric parameters from a GPS reanalysis carried out in a common project of the Technical Universities in Munich and Dresden were converted into precipitable water (PW) using surface pressure observations from the WMO and mean atmospheric temperature data from ECMWF. PW time series were generated for 141 globally distributed GPS sites covering the time period from the beginning of 1994 to the end of 2004. The GPS-derived PW time series were carefully examined for their homogeneity. The validation of the NWP model from NCEP shows that the differences between the modeled and observed PW values are time dependent. In addition to establishing a long-term mean, this study also validates the seasonal cycle and interannual variations in the PW. Over Europe and large parts of North America the seasonal cycle and the interannual variations in the PW from GPS and NCEP agree very well. The results reveal a submillimeter accuracy of the GPS-derived PW anomalies. In the regions mentioned above, NCEP provides a highly accurate database for studies of long-term changes in the atmospheric water vapor. However, in the Southern Hemisphere large differences in the seasonal signals and in the PW anomalies were found between GPS and NCEP. The seasonal signal of the PW is underestimated by NCEP in the tropics and in Antarctica by up to 40% and 25%, respectively. Climate change studies based on water vapor data from NCEP should consider the large uncertainties in the analysis when interpreting these data, especially in the tropics.
The Influence of the Basic State on the Northern Hemisphere Circulation Response to Climate Change
Authors: Sigmond Michael , Scinocca John F. 
Published: November 2009

Abstract
Employing a comprehensive atmospheric general circulation model, the authors have shown in a previous study that the time-mean Northern Hemisphere (NH) winter circulation response to a CO2 doubling perturbation depends significantly on parameterized orographic gravity wave drag (OGWD) parameter settings, which are essentially related to the strength of OGWD. A possible implication is that aspects of the greenhouse gas–induced circulation response could depend directly on the formulation and internal parameters settings of the OGWD scheme. Such a result would further heighten the importance of OGWD parameterizations for climate studies and have far-reaching implications for modeled projections of future climate change.
In this study the causal relationship between OGWD and changes in time-mean NH wintertime circulation response to CO2 doubling is investigated. This is accomplished by introducing a methodology that allows one to hold the OGWD forcing fixed to its 1 × CO2 value when CO2 is doubled. Employing this methodology for perturbation experiments with different strengths of OGWD, the authors find that the changes in OGWD forcing due to CO2 doubling have essentially no impact on the time-mean zonal-mean zonal wind response. The primary conclusion is that the OGWD influence is limited to its impact on the 1 × CO2 basic-state climatology, which defines the propagation characteristics of resolved waves. Different strengths of OGWD result in control basic states with different refractive properties for the resolved waves. It is shown that the action of resolved waves, as well as their sensitivity to such differences in the control climatology, explains essentially all of the NH wintertime circulation sensitivity identified here and in a previous study. Implications for climate change projections and climate-model development are discussed.
Comparative gene expression analysis of zebrafish and mammals identifies common regulators in hematopoietic stem cells
Authors: Kobayashi Isao , Ono Hiromasa , Moritomo Tadaaki , Kano Koichiro , Nakanishi Teruyuki , Suda Toshio 
Published: November 2009

AbstractHematopoiesis in teleost fish is maintained in the kidney. We previously reported that Hoechst dye efflux activity of hematopoietic stem cells (HSCs) is highly conserved in vertebrates, and that Hoechst can be used to purify HSCs from teleost kidneys. Regulatory molecules that are strongly associated with HSC activity may also be conserved in vertebrates. In this study, we identified evolutionarily conserved molecular components in HSCs by comparing the gene expression profiles of zebrafish, murine, and human HSCs. Microarray data of zebrafish kidney side population cells (zSPs) showed that genes involved in cell junction and signal transduction tended to be up-regulated in zSPs, whereas genes involved in DNA replication tended to be down-regulated. These properties of zSPs were similar to those of mammalian HSCs. Overlapping gene expression analysis showed that 40 genes were commonly up-regulated in these 3 HSCs. Some of these genes, such as egr1, gata2, and id1, have been previously implicated in the regulation of HSCs. In situ hybridization in zebrafish kidney revealed that expression domains of egr1, gata2, and id1 overlapped with that of abcg2a, a marker for zSPs. These results suggest that the overlapping genes identified in this study are regulated in HSCs and play important roles in their functions.