bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Viral Factor E3L in Modified Vaccinia Virus Ankara Infection of Human HeLa Cells: Regulation of the Virus Life Cycle and Identification of Differentially Expressed Host Genes
Authors: Ludwig Holger , Mages Jörg , Staib Caroline , Lehmann Michael H. , Lang Roland , Sutter Gerd 
Published: January 2005

ABSTRACT
Modified vaccinia virus Ankara (MVA) is a highly attenuated virus strain being developed as a vaccine for delivery of viral and recombinant antigens. The MVA genome lacks functional copies of numerous genes interfering with host response to infection. The interferon resistance gene E3L encodes one important viral immune defense factor still made by MVA. Here we demonstrate an essential role of E3L to allow for completion of the MVA molecular life cycle upon infection of human HeLa cells. A deletion mutant virus, MVA-ΔE3L, was found defective in late protein synthesis, viral late transcription, and viral DNA replication in infected HeLa cells. Moreover, we detected viral early and continuing intermediate transcription associated with degradation of rRNA, indicating rapid activation of 2′-5′-oligoadenylate synthetase/RNase L in the absence of E3L. Further molecular monitoring of E3L function by microarray analysis of host cell transcription in MVA- or MVA-ΔE3L-infected HeLa cells revealed an overall significant down regulation of more than 50% of cellular transcripts expressed under mock conditions already at 5 h after infection, with a more prominent shutoff following MVA-ΔE3L infection. Interestingly, a cluster of genes up regulated exclusively in MVA-ΔE3L-infected cells could be identified, including transcripts for interleukin 6, growth arrest and DNA damage-inducible protein β, and dual-specificity protein phosphatases. Our data indicate that lack of E3L inhibits MVA antigen production in human HeLa cells at the level of viral late gene expression and suggest that E3L can prevent activation of additional host factors possibly affecting the MVA molecular life cycle.
Inhibition of Cell Division by the Human Cytomegalovirus IE86 Protein: Role of the p53 Pathway or Cyclin-Dependent Kinase 1/Cyclin B1
Authors: Song Yoon-Jae , Stinski Mark F. 
Published: January 2005

ABSTRACT

The human cytomegalovirus (HCMV) IE86 protein induces the human fibroblast cell cycle from G
0
/G
1
to G
1
/S, where cell cycle progression stops. Cells with a wild-type, mutated, or null p53 or cells with null p21 protein were transduced with replication-deficient adenoviruses expressing HCMV IE86 protein or cellular p53 or p21. Even though S-phase genes were activated in a p53 wild-type cell, IE86 protein also induced phospho-Ser
15
p53 and p21 independent of p14ARF but dependent on ATM kinase. These cells did not enter the S phase. In human p53 mutant, p53 null, or p21 null cells, IE86 protein did not up-regulate p21, cellular DNA synthesis was not inhibited, but cell division was inhibited. Cells accumulated in the G
2
/M phase, and there was increased cyclin-dependent kinase 1/cyclin B1 activity. Although the HCMV IE86 protein increases cellular E2F activity, it also blocks cell division in both p53
+/+
and p53
−/−
cells.
Early Steps of Clathrin-Mediated Endocytosis Involved in Phagosomal Escape of Fcγ Receptor-Targeted Adenovirus
Authors: Meier Oliver , Gastaldelli Michele , Boucke Karin , Hemmi Silvio , Greber Urs F. 
Published: January 2005

ABSTRACTAdenovirus type 2 (Ad2) and Ad5 enter epithelial cells via the coxsackievirus B Ad receptor (CAR) and αvintegrin coreceptors. In the absence of CAR, they can be directed to the Fcγ receptor 1 of hematopoietic cells by an adaptor comprising the extracellular CAR domain and the Fc portion of a human immunoglobulin G (CARex-Fc). This gives rise to Ad aggregates and single particles which together enhance gene delivery up to 250-fold compared to adaptor-less viruses. A small interfering RNA knockdown of the clathrin heavy chain and quantitative electron microscopy of hematopoietic leukemia cells showed that the majority of Ads were phagocytosed as clusters of 1 to 3 μm in diameter and that about 10% of the particles entered cells by clathrin-mediated endocytosis. The clathrin knockdown did not affect phagocytosis but, surprisingly, inhibited viral escape from phagosomes. Similarly, blocking an early stage of clathrin-coated pit assembly inhibited phagosomal escape and infection but not aggregate uptake, unlike blocking of a late stage of clathrin-coated pit formation. We propose a cooperative interaction of clathrin-mediated endocytosis and phagocytosis triggering phagosomal lysis and infection.
Civets Are Equally Susceptible to Experimental Infection by Two Different Severe Acute Respiratory Syndrome Coronavirus Isolates
Authors: Wu Donglai , Tu Changchun , Xin Chaoan , Xuan Hua , Meng Qingwen , Liu Yonggang , Yu Yedong , Guan Yuntao , Jiang Yu , Yin Xunnan , Crameri Gary , Wang Muping , Li Changwen , Liu Shengwang , Liao Ming , Feng Li , Xiang Hua , Sun Jinfu , Chen Jinding , Sun Yanwei , Gu Shoulin , Liu Nihong , Fu Dexia , Eaton Bryan T. , Wang Lin-Fa , Kong Xiangang 
Published: January 2005

ABSTRACT

Severe acute respiratory syndrome (SARS) was caused by a novel virus now known as SARS coronavirus (SARS-CoV). The discovery of SARS-CoV-like viruses in masked palm civets (
Paguma larvata
) raises the possibility that civets play a role in SARS-CoV transmission. To test the susceptibility of civets to experimental infection by different SARS-CoV isolates, 10 civets were inoculated with two human isolates of SARS-CoV, BJ01 (with a 29-nucleotide deletion) and GZ01 (without the 29-nucleotide deletion). All inoculated animals displayed clinical symptoms, such as fever, lethargy, and loss of aggressiveness, and the infection was confirmed by virus isolation, detection of viral genomic RNA, and serum-neutralizing antibodies. Our data show that civets were equally susceptible to SARS-CoV isolates GZ01 and BJ01.
Characterization of the Minimal Replicator of Kaposi's Sarcoma-Associated Herpesvirus Latent Origin
Authors: Hu Jianhong , Renne Rolf 
Published: January 2005

ABSTRACT
The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) binds to two sites within the 801-bp-long terminal repeat (TR) and is the only viral protein required for episomal maintenance. While two or more copies of TR are required for long-term maintenance, a single TR confers LANA-dependent origin activity on plasmid DNA. Deletion mapping revealed a 71-bp-long minimal replicator containing two distinctive sequence elements: LANA binding sites (LBS1/2) and an adjacent 29- to 32-bp-long GC-rich sequence which we termed the replication element. Furthermore, the transcription factor Sp1 can bind to TR outside the minimal replicator and contributes to TR's previously reported enhancer activity.
The role of tourist icons for sustainable tourism
Authors: Becken Susanne 
Published: January 2005

This paper provides a discussion of tourist icons as pull factors of a destination and problems associated with icons. According to interviews held with major wholesalers in Australia and inbound tour operators in New Zealand, tourist icons vary in importance to different segments of the market, with coach tourists placing more importance on icons than free independent travellers. Moreover, the need to base overseas marketing on icons depends on the maturity of the targeted market. A tourist survey in New Zealand revealed that Milford Sound and Rotorua were indeed the most commonly known attractions, but that in addition to these two key icons, tourists were attracted to natural features in general, such as mountains and glaciers. This paper argues that an overemphasis on tourist icons potentially leads to unsustainable tourism development, for the following reasons: tourists travel large distances to visit the spatially very dispersed tourist icons, and this results in considerable amounts of greenhouse gas emissions, even if they visit New Zealand for a short period of time; the high visitation levels at popular sites result in infrastructural bottlenecks, reaching carrying capacity, which results in potentially significant environmental and social impacts; and the uneven geographical distribution of tourism spending is a missed opportunity for much-needed regional development. The current ‘100% Pure’ campaign by Tourism New Zealand potentially contributes to a more holistic promotion of New Zealand as an attractive ‘natural landscape’ destination.
The detailed structure and origin of clay minerals at the Cretaceous/Tertiary boundary, Stevns Klint (Denmark)
Authors: Drits V. A. , Lindgreen H. , Sakharov B. A. , Jakobsen H. J. , Zviagina B. B. 
Published: January 2005

AbstractThe structure of an illite-smectite (I-S) sample (HSI) from the Tertiary–Cretaceous boundary layer at Stevns, Denmark, i.e. the so-called Fish Clay, is investigated in order to discuss the origin of this clay and its similarity to clays from Maastrichtian-Danian chalk of Denmark and the North Sea. The phase compositions and layer sequences have been determined by X-ray diffraction. The structural formulae are determined from chemical analysis and solid-state 27Al magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The octahedral vacancy pattern has been determined by thermal analysis and the particle shape by atomic force microscopy. The HSI sample I-S consists of two phases, a high-smectitic (HS) phase (70%) having 95% smectite and 5% illite (leucophyllite) layers, and a low-smectitic (LS) phase (30%) having 50% smectite and 50% illite (leucophyllite) layers. Both phases have trans-vacant dioctahedral sheets and contain only traces of IVAl, the charge of the illite (leucophyllite) layers being provided predominantly by octahedral Mg for Al substitution. The structure of the tetrahedral and octahedral sheets for the HSI are compared to the structure of an I-S sample (GRI) from the Maastrichtian chalk at Stevns below the Tertiary-Cretaceous boundary and to the standard smectite SAz-1 from Arizona. For all three samples the 27Al MAS NMR spectra show the presence of two resolved IVAl resonances, which indicate the presence of two different IVAl sites. The NMR, infrared spectroscopy and chemical data show that both HSI and GRI have highly ordered Mg for Al substitution in the octahedral sheet, each Al having one Mg and two Al neighbours, whereas substitution of Mg for Al in SAz-1 is random. For the HSI sample, both the HS and LS phases are probably formed from volcanic ash. The structural similarity of the phases in HSI and GRI shows that GRI formed from a material similar to HSI by illitization of the HS phase and chloritization of the LS phase.
In situ transformation of amorphous gels into spherical aggregates of kaolinite: A HRTEM study
Authors: Huertas F. J. , Fiore S. , Linares J. 
Published: January 2005

AbstractInitial stages of the gel-to-kaolinite transformation were studied using HRTEM. Spherical aggregates of kaolinite crystals were produced during the synthesis of kaolinite by hydrothermal treatment of Si-Al amorphous gels. Prior to sphere formation, gels transform into pseudospherical domains that have a Si/Al ratio of one and display no SAED pattern. The spherical particles consist of radially arranged sectors of stacks of planar crystallites. Crystals display nonbasal spacings of 4.5, 4.2 and 3.8 Å and a basal spacing of 7.1 Å , the c* axis following the radius of the sphere.Interpretation of the 3D nanostructure of the spheres is difficult. The c* axis exhibits a radial disposition, but the relative orientation of the a* and b* axes in neighbouring crystallites may produce bent layers or incoherent contacts. In addition, curved layers with a d spacing of 7.4 Å may be attributed to halloysite layers collapsed under microscopy conditions. The disappearance of the spheres during the hydrothermal treatment is probably due to preferential dissolution of either highstress areas near bent layers or non-crystalline material filling crystal boundaries. Dissolution leads to sphere disaggregation and allows the component columnar crystals to continue to grow. Observations of the gel matrix suggest that under our experimental conditions kaolinite crystallizes via an in situ transformation of the gel.
Experimental study of swelling in unsaturated compacted clays
Authors: Saiyouri N. , Tessier D. , Hicher P. Y. 
Published: January 2005

AbstractThis paper describes the swelling properties of two highly compacted clays, natural, untreated Wyoming montmorillonite (MX80) and Fourges smectite (FoCa7), saturated with Na and Ca, respectively.The initially compacted samples were hydrated by subjecting them to different suction pressures in a range between 100 MPa and 1 kPa. For each equilibrium state, the volume change (swelling) and water content (hydration) were measured. The samples were then studied by X-ray diffraction using a transmission device to determine interlayer distance and particle size, in order to clarify both the swelling and hydration mechanisms. The distances between clay layers ranged between 10 and 21.6 Å , i.e. corresponding to between 0 and 4 water layers. Upon hydration, the particle size decreased from 350 and 100 clay layers per particle to 10 layers per particle when the suction pressure decreased from 100 MPa to 1 kPa for MX80 and FoCa7, respectively. The first swelling stage is described as being an insertion of water molecules between the layers. Then a division of the initial particles into particles of smaller size with increasingly large inter-particle distances was observed. Observations by transmission electronic microscopy confirmed these results.
Diagenetic to low-grade metamorphic evolution of clay mineral assemblages in Palaeozoic to early Mesozoic rocks of the Eastern Taurides, Turkey
Authors: Bozkaya Ö. , Yalçin H. 
Published: January 2005

AbstractPalaeozoic to early Mesozoic rocks of both autochthonous and allochthonous units of the Eastern Tauride Belt have different textural and mineralogical features related to their varying deposition regimes and thermal histories. The Devonian and Carboniferous formations in the allocthonous units have anchizonal to epizonal grades of metamorphism, whereas those of the autochthon experienced only early diagenetic conditions. A well-developed penetrative slaty cleavage is also found in Devonian formations of the allocthonous units, which is not observed in equivalent rocks of the autochthon. Phyllosilicates of the uncleaved diagenetic assemblages consist mainly of illite, chlorite, kaolinite, mixed-layer illite-smectite, chlorite-vermiculite and chloritesmectite, whereas in addition to these, metamorphic allochthonous units contain some index minerals such as dickite, paragonite, Na and K mica, pyrophyllite, stilpnomelane and chloritoid. These latter assemblages show a higher degree of textural and mineralogical maturation and lower b cell dimensions than the autochthonous rocks, suggesting that they originated in a relatively high heat flow basin such as an extensional setting.
Effectiveness of different databases in identifying studies for systematic reviews: experience from the WHO systematic review of maternal morbidity and mortality
Authors: Betrán Ana P , Say Lale , Gülmezoglu A Metin , Allen Tomas , Hampson Lynn 
Published: January 2005

Abstract
Background
Failure to be comprehensive can distort the results of a systematic review. Conversely, extensive searches may yield unmanageable number of citations of which only few may be relevant. Knowledge of usefulness of each source of information may help to tailor search strategies in systematic reviews.

Methods
We conducted a systematic review of prevalence/incidence of maternal mortality and morbidities from 1997 to 2002. The search strategy included electronic databases, hand searching, screening of reference lists, congress abstract books, contacting experts active in the field and web sites from less developed countries. We evaluated the effectiveness of each source of data and discuss limitations and implications for future research on this topic.

Results
Electronic databases identified 64098 different citations of which 2093 were included. Additionally 487 citations were included from other sources. MEDLINE had the highest yield identifying about 62% of the included citations. BIOSIS was the most precise with 13.2% of screened citations included. Considering electronic citations alone (2093), almost 20% were identified uniquely by MEDLINE (400), 7.4% uniquely by EMBASE (154), and 5.6% uniquely by LILACS (117). About 60% of the electronic citations included were identified by two or more databases.

Conclusions
This analysis confirms the need for extending the search to other sources beyond well-known electronic databases in systematic reviews of maternal mortality and morbidity prevalence/incidence. These include regional databases such as LILACS and other topic specific sources such as hand searching of relevant journals not indexed in electronic databases. Guidelines for search strategies for prevalence/incidence studies need to be developed.
Injury morbidity in an urban and a rural area in Tanzania: an epidemiological survey
Authors: Moshiro Candida , Heuch Ivar , Åstrøm Anne Nordrehaug , Setel Philip , Hemed Yusuf , Kvåle Gunnar 
Published: January 2005

Abstract
Background
Injuries are becoming a major health problem in developing countries. Few population based studies have been carried out in African countries. We examined the pattern of nonfatal injuries and associated risk factors in an urban and rural setting of Tanzania.

Methods
A population-based household survey was conducted in 2002. Participants were selected by cluster sampling. A total of 8,188 urban and 7,035 rural residents of all ages participated in the survey. All injuries reported among all household members in the year preceding the interview and resulting in one or more days of restricted activity were included in the analyis.

Results
A total of 206 (2.5%) and 303 (4.3%) persons reported to have been injured in the urban and rural area respectively. Although the overall incidence was higher in the rural area, the incidence of major injuries (≥ 30 disability days) was similar in both areas. Males were at a higher risk of having an injury than females. Rural residents were more likely to experience injuries due to falls (OR = 1.6; 95% CI = 1.1 – 2.3) and cuts (OR = 4.3; 95% CI = 3.0 – 6.2) but had a lower risk of transport injuries. The most common causes of injury in the urban area were transport injuries and falls. In the rural area, cuts and stabs, of which two thirds were related to agriculture, formed the most common cause. Age was an important risk factor for certain types of injuries. Poverty levels were not significantly associated with experiencing a nonfatal injury.

Conclusion
The patterns of injury differ in urban and rural areas partly as a reflection of livelihoods and infrastructure. Rural residents are at a higher overall injury risk than urban residents. This may be important in the development of injury prevention strategies.
The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice
Authors: Liu Ji-Yan , Zhang Xiao-Shi , Ding Ya , Peng Rui-Qing , Cheng Xia , Zhang Nian-Hua , Xia Jian-Chuan , Zeng Yi-Xin 
Published: January 2005

AbstractCD4+CD25+ regulatory T lymphocytes (TR) constitute 5–10% of peripheral CD4+ T cells in naive mice and humans, and play an important role in controlling immune responses. Accumulating evidences show that TR cells are involved in some physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer, and might be a promising therapeutic target for these diseases.To evaluate the change of CD4+CD25+ TR cells in mouse tumor models, CD4+CD25+ subset in peripheral blood and spleen lymphocytes from normal or C26 colon-carcinoma-bearing BABL/c mice were analyzed by flow cytometry using double staining with CD4 and CD25 antibodies.The proportion of CD4+CD25+/CD4+ in spleen lymphocytes was found to be higher than that in peripheral blood lymphocytes in normal mice. No difference was observed in the proportion in peripheral blood lymphocytes between tumor bearing mice and normal mice, while there was a significant increase in the proportion in spleen lymphocytes in tumor bearing mice as compared with normal mice. Moreover, the proportion increased in accordance with the increase in the tumor sizes. The increase in the proportion was due to the decrease in CD4+ in lymphocytes, which is resulted from decreased CD4+CD25- subset in lymphocytes. Our observation suggests the CD4+CD25+/CD4+ proportion in spleen lymphocytes might be a sensitive index to evaluate the TR in tumor mouse models, and our results provide some information on strategies of antitumor immunotherapy targeting CD4+CD25+ regulatory T lymphocytes.
Comparative analysis of protein coding sequences from human, mouse and the domesticated pig
Authors: Jørgensen Frank Grønlund , Hobolth Asger , Hornshøj Henrik , Bendixen Christian , Fredholm Merete , Schierup Mikkel Heide 
Published: January 2005

Abstract

Background

The availability of abundant sequence data from key model organisms has made large scale studies of molecular evolution an exciting possibility. Here we use full length cDNA alignments comprising more than 700,000 nucleotides from human, mouse, pig and the Japanese pufferfish Fugu rubrices in order to investigate 1) the relationships between three major lineages of mammals: rodents, artiodactyls and primates, and 2) the rate of evolution and the occurrence of positive Darwinian selection using codon based models of sequence evolution.

Results

We provide evidence that the evolutionary splits among primates, rodents and artiodactyls happened shortly after each other, with most gene trees favouring a topology with rodents as outgroup to primates and artiodactyls. Using an unrooted topology of the three mammalian species we show that since their diversification, the pig and mouse lineages have on average experienced 1.44 and 2.86 times as many synonymous substitutions as humans, respectively, whereas the rates of non-synonymous substitutions are more similar. The analysis shows the highest average dN/dS ratio in the human lineage, followed by the pig and then the mouse lineages. Using codon based models we detect signals of positive Darwinian selection in approximately 5.3%, 4.9% and 6.0% of the genes on the human, pig and mouse lineages respectively. Approximately 16.8% of all the genes studied here are not currently annotated as functional genes in humans. Our analyses indicate that a large fraction of these genes may have lost their function quite recently or may still be functional genes in some or all of the three mammalian species.

Conclusions

We present a comparative analysis of protein coding genes from three major mammalian lineages. Our study demonstrates the usefulness of codon-based likelihood models in detecting selection and it illustrates the value of sequencing organisms at different phylogenetic distances for comparative studies.