bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-Specific Cellular Immune Correlates of Survival in Vaccinated Monkeys after Simian Immunodeficiency Virus Challenge
Authors: Sun Yue , Schmitz Jörn E. , Buzby Adam P. , Barker Brianne R. , Rao Srinivas S. , Xu Ling , Yang Zhi-yong , Mascola John R. , Nabel Gary J. , Letvin Norman L. 
Published: October 2006

ABSTRACT

Understanding the characteristics of the virus-specific T-lymphocyte response that will confer optimal protection against the clinical progression of AIDS will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4
+
T lymphocytes and robust gamma interferon (IFN-γ)-producing SIV-specific CD8
+
and CD4
+
T-lymphocyte responses. The present studies were initiated to extend these observations to determine which virus-specific T-lymphocyte subpopulations play a primary role in controlling disease progression and to characterize the functional repertoire of these cells. We show that the preservation of the SIV-specific central memory CD8
+
T-lymphocyte population and a linked SIV-specific CD4
+
T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge. Furthermore, we demonstrate that SIV-specific IFN-γ-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression. These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection.
Crystal Structure of West Nile Virus Envelope Glycoprotein Reveals Viral Surface Epitopes
Authors: Kanai Ryuta , Kar Kalipada , Anthony Karen , Gould L. Hannah , Ledizet Michel , Fikrig Erol , Marasco Wayne A. , Koski Raymond A. , Modis Yorgo 
Published: October 2006

ABSTRACT

West Nile virus
, a member of the
Flavivirus
genus, causes fever that can progress to life-threatening encephalitis. The major envelope glycoprotein, E, of these viruses mediates viral attachment and entry by membrane fusion. We have determined the crystal structure of a soluble fragment of West Nile virus E. The structure adopts the same overall fold as that of the E proteins from dengue and tick-borne encephalitis viruses. The conformation of domain II is different from that in other prefusion E structures, however, and resembles the conformation of domain II in postfusion E structures. The epitopes of neutralizing West Nile virus-specific antibodies map to a region of domain III that is exposed on the viral surface and has been implicated in receptor binding. In contrast, we show that certain recombinant therapeutic antibodies, which cross-neutralize West Nile and dengue viruses, bind a peptide from domain I that is exposed only during the membrane fusion transition. By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics.
A High-Throughput Method for Cloning and Sequencing Human Immunodeficiency Virus Type 1 Integration Sites
Authors: Kim Sanggu , Kim Yein , Liang Teresa , Sinsheimer Janet S. , Chow Samson A. 
Published: October 2006

ABSTRACT
Integration of retroviral DNA is nonspecific and can occur at many sites throughout chromosomes. However, the process is not uniformly distributed, and both hot and cold spots for integration exist. The mechanism that determines target site specificity is not well understood. Because of the nonspecific and widespread nature of integration, studies analyzing the mechanism and factors that control target site selection require the collection and analysis of a large library of human immunodeficiency virus type 1 (HIV-1) proviral clones. Such analyses are time-consuming and labor-intensive using conventional means. We have developed an efficient and high-throughput method of sequencing and mapping a large number of independent integration sites in the absence of any selection or bias. The new assay involves the use of a modified HIV-1 (NL-Mme) containing a type IIS restriction site, MmeI, at the right end of viral DNA. Digestion of genomic DNA from NL-Mme-infected cells generated viral DNA-containing fragments of a discrete size. Subsequent ligation-mediated PCR yielded short integration site fragments termed Int-tags, which were concatemerized for determining multiple integration sites in a single sequencing reaction. Analysis of chromosomal features and sequence preference associated with integration events confirmed the validity of the new high-throughput assay. The assay will aid the effort in understanding the mechanisms of target site selection during HIV-1 DNA integration, and the described methodology can be adapted easily to integration site studies involving other retroviruses and transposons.
The C-Terminal Hydrophobic Domain of Hepatitis C Virus RNA Polymerase NS5B Can Be Replaced with a Heterologous Domain of Poliovirus Protein 3A
Authors: Lee Haekyung , Liu Ying , Mejia Edison , Paul Aniko V. , Wimmer Eckard 
Published: October 2006

ABSTRACT
Replication of the plus-stranded RNA genome of hepatitis C virus (HCV) occurs in a membrane-bound replication complex consisting of viral and cellular proteins and viral RNA. NS5B, the RNA polymerase of HCV, is anchored to the membranes via a C-terminal 20-amino-acid-long hydrophobic domain, which is flanked on each side by a highly conserved positively charged arginine. Using a genotype 1b subgenomic replicon (V. Lohmann, F. Korner, J. O. Koch, U. Herian, L. Theilmann, and R. Bartensclager, Science 285:110-113, 1999), we determined the effect of mutations of some highly conserved residues in this domain. The replacement of arginine 570 with alanine completely abolished the colony-forming ability by the replicon, while a R591A change was found to be highly detrimental to replication, viability, and membrane binding by the mutant NS5B protein. Mutations of two other highly conserved amino acids (L588A and P589A) reduced but did not eliminate colony formation. It was of interest, if specific amino acid residues play a role in membrane anchoring of NS5B and replication, to determine whether a complete exchange of the NS5B hydrophobic domain with a domain totally unrelated to NS5B would ablate replication. We selected the 22-amino-acid-long hydrophobic domain of poliovirus polypeptide 3A that is known to adopt a transmembrane configuration, thereby anchoring 3A to membranes. Surprisingly, either partial or full replacement of the NS5B hydrophobic domain with the anchor sequences of poliovirus polypeptide 3A resulted in the replication of replicons whose colony-forming abilities were reduced compared to that of the wild-type replicon. Upon continued passage of the replicon in Huh-7 cells in the presence of neomycin, the replication efficiency of the replicon increased. However, the sequence of the poliovirus polypeptide 3A hydrophobic domain, in the context of the subgenomic HCV replicon, was stably maintained throughout 40 passages. Our results suggest that anchoring NS5B to membranes is necessary but that the amino acid sequence of the anchor per se does not require HCV origin. This suggests that specific interactions between the NS5B hydrophobic domain and other membrane-bound factors may not play a decisive role in HCV replication.
Truncating Variants in p53AIP1 Disrupting DNA Damage–Induced Apoptosis Are Associated with Prostate Cancer Risk
Authors: Wang Xianshu , Wang Fengwei , Taniguchi Ken , Seelan Ratnam S. , Wang Liang , Zarfas Katherine E. , McDonnell Shannon K. , Qian Chiping , Pan Kaifeng , Lu Youyong , Shridhar Viji , Couch Fergus J. , Tindall Donald J. , Beebe-Dimmer Jennifer L. , Cooney Kathleen A. , Isaacs William B. , Jacobsen Steven J. , Schaid Daniel J. , Thibodeau Stephen N. , Liu Wanguo 
Published: November 2006

Abstract
Germ line mutations in several genes (BRCA1, BRCA2, and CHEK2) whose products are involved in the DNA damage–signaling pathway have been implicated in prostate cancer risk. To identify additional genes in this pathway that might confer susceptibility to this cancer, we analyzed a recently identified DNA damage–response gene, p53AIP1 (a gene encoding for p53-regulated apoptosis-inducing protein 1), for genetic variants in prostate cancer. Five novel germ line variants were identified. The two truncating variants (Ser32Stop and Arg21insG) were found in 3% (4 of 132) of unselected prostate tumor samples. Genotyping of the two variants in an additional 393 men with sporadic prostate cancer showed a frequency of 3.1% (12 of 393) in contrast to 0.6% (2 of 327) in 327 unaffected men (Fisher's exact test, P = 0.018), with an odds ratio (OR) of 5.1 [95% confidence interval (95% CI), 1.1-23.0]. In addition, two of six tumors carrying the truncating variants were associated with loss of heterozygosity of the wild-type alleles, suggesting that p53AIP1 may act as a tumor suppressor. We also showed that the truncated p53AIP1 was unable to induce apoptosis and suppress cell growth in HeLa and COS-7 cells. These results suggest that loss-of-function variants in p53AIP1 associated with the risk of sporadic prostate cancer and further support the concept that the genetic defects in the DNA damage–response genes play an important role in the development of prostate cancer. (Cancer Res 2006; 66(21): 10302-7)
Examination of a CpG Island Methylator Phenotype and Implications of Methylation Profiles in Solid Tumors
Authors: Marsit Carmen J. , Houseman E. Andres , Christensen Brock C. , Eddy Karen , Bueno Raphael , Sugarbaker David J. , Nelson Heather H. , Karagas Margaret R. , Kelsey Karl T. 
Published: November 2006

Abstract
The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to a lesser extent in other solid tumors, is important in understanding epigenetics in carcinogenesis and may be clinically useful for classification of neoplastic disease. Therefore, we investigated whether this putative phenotype exists in exposure-related solid tumors, where somatic gene alterations and enhanced clonal growth are selected for by carcinogens, and examined the ability of methylation profiles to classify malignant disease. We studied promoter hypermethylation of 16 tumor suppressor genes and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous cell carcinomas (HNSCC), 146 non–small-cell lung cancer (NSCLC), and 71 malignant pleural mesotheliomas (MPM). We employed rigorous statistical methods to examine the distribution of promoter methylation and the usefulness of these profiles for disease classification. In bladder cancer, HNSCC, and NSCLC, there was a significant correlation (P &lt; 0.0001) between methylation of the three MINT loci and methylation index, although the distribution of methylated loci varied significantly across these disease. Although there was a significant (P &lt; 0.001) association between gene methylation profile and disease, rates of misclassification of each disease by their methylation profile ranged from 28% to 32%, depending on the classification scheme used. These data suggest that a form of CIMP exists in these solid tumors, although its etiology remains elusive. Whereas the gene profiles of hypermethylation among examined loci could not unequivocally distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation in these cancers suggest that methylation analysis may be clinically useful as a targeted screening tool. (Cancer Res 2006; 66(21): 10621-9)
Topological basis of signal integration in the transcriptional-regulatory network of the yeast, Saccharomyces cerevisiae
Authors: Farkas Illés J , Wu Chuang , Chennubhotla Chakra , Bahar Ivet , Oltvai Zoltán N 
Published: October 2006

Abstract

Background
Signal recognition and information processing is a fundamental cellular function, which in part involves comprehensive transcriptional regulatory (TR) mechanisms carried out in response to complex environmental signals in the context of the cell's own internal state. However, the network topological basis of developing such integrated responses remains poorly understood.

Results
By studying the TR network of the yeast Saccharomyces cerevisiae we show that an intermediate layer of transcription factors naturally segregates into distinct subnetworks. In these topological units transcription factors are densely interlinked in a largely hierarchical manner and respond to external signals by utilizing a fraction of these subnets.

Conclusion
As transcriptional regulation represents the 'slow' component of overall information processing, the identified topology suggests a model in which successive waves of transcriptional regulation originating from distinct fractions of the TR network control robust integrated responses to complex stimuli.
Bifidobacterium infantisstrains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats
Authors: Osman Nadia , Adawi Diya , Molin Göran , Ahrne Siv , Berggren Anna , Jeppsson Bengt 
Published: October 2006

Abstract

Background
Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit.

Methods
Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1β, TNF-α, IL-10 and TGF-β) and malondialdehyde (MDA).

Results
OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups.

Conclusion
Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations.
Multiple, non-allelic, intein-coding sequences in eukaryotic RNA polymerase genes
Authors: Goodwin Timothy JD , Butler Margaret I , Poulter Russell TM 
Published: October 2006

Abstract

Background

Inteins are self-splicing protein elements. They are translated as inserts within host proteins that excise themselves and ligate the flanking portions of the host protein (exteins) with a peptide bond. They are encoded as in-frame insertions within the genes for the host proteins. Inteins are found in all three domains of life and in viruses, but have a very sporadic distribution. Only a small number of intein coding sequences have been identified in eukaryotic nuclear genes, and all of these are from ascomycete or basidiomycete fungi.

Results

We identified seven intein coding sequences within nuclear genes coding for the second largest subunits of RNA polymerase. These sequences were found in diverse eukaryotes: one is in the second largest subunit of RNA polymerase I (RPA2) from the ascomycete fungus Phaeosphaeria nodorum, one is in the RNA polymerase III (RPC2) of the slime mould Dictyostelium discoideum and four intein coding sequences are in RNA polymerase II genes (RPB2), one each from the green alga Chlamydomonas reinhardtii, the zygomycete fungus Spiromyces aspiralis and the chytrid fungi Batrachochytrium dendrobatidis and Coelomomyces stegomyiae. The remaining intein coding sequence is in a viral relic embedded within the genome of the oomycete Phytophthora ramorum. The Chlamydomonas and Dictyostelium inteins are the first nuclear-encoded inteins found outside of the fungi.
These new inteins represent a unique dataset: they are found in homologous proteins that form a paralogous group. Although these paralogues diverged early in eukaryotic evolution, their sequences can be aligned over most of their length. The inteins are inserted at multiple distinct sites, each of which corresponds to a highly conserved region of RNA polymerase. This dataset supports earlier work suggesting that inteins preferentially occur in highly conserved regions of their host proteins.

Conclusion

The identification of these new inteins increases the known host range of intein sequences in eukaryotes, and provides fresh insights into their origins and evolution. We conclude that inteins are ancient eukaryote elements once found widely among microbial eukaryotes. They persist as rarities in the genomes of a sporadic array of microorganisms, occupying highly conserved sites in diverse proteins.
Efficacy and safety of a low-flow veno-venous carbon dioxide removal device: results of an experimental study in adult sheep
Authors: Livigni Sergio , Maio Mariella , Ferretti Enrica , Longobardo Annalisa , Potenza Raffaele , Rivalta Luca , Selvaggi Paola , Vergano Marco , Bertolini Guido 
Published: October 2006

Abstract
Introduction
Extracorporeal lung assist, an extreme resource in patients with acute respiratory failure (ARF), is expanding its indications since knowledge about ventilator-induced lung injury has increased and protective ventilation has become the standard in ARF.

Methods
A prospective study on seven adult sheep was conducted to quantify carbon dioxide (CO2) removal and evaluate the safety of an extracorporeal membrane gas exchanger placed in a veno-venous pump-driven bypass. Animals were anaesthetised, intubated, ventilated in order to reach hypercapnia, and then connected to the CO2 removal device. Five animals were treated for three hours, one for nine hours, and one for 12 hours. At the end of the experiment, general anaesthesia was discontinued and animals were extubated. All of them survived.

Results
No significant haemodynamic variations occurred during the experiment. Maintaining an extracorporeal blood flow of 300 ml/minute (4.5% to 5.3% of the mean cardiac output), a constant removal of arterial CO2, with an average reduction of 17% to 22%, was observed. Arterial partial pressure of carbon dioxide (PaCO2) returned to baseline after treatment discontinuation. No adverse events were observed.

Conclusion
We obtained a significant reduction of PaCO2 using low blood flow rates, if compared with other techniques. Percutaneous venous access, simplicity of circuit, minimal anticoagulation requirements, blood flow rate, and haemodynamic impact of this device are more similar to renal replacement therapy than to common extracorporeal respiratory assistance, making it feasible not only in just a few dedicated centres but in a large number of intensive care units as well.
Out on a limb: the differential effect of substrate diameter on acceleration capacity inAnolislizards
Authors: Vanhooydonck Bieke , Herrel Anthony , Irschick Duncan J. 
Published: November 2006

SUMMARYWe investigated how substrate diameter affects acceleration performance in three Anolis lizard species (A. sagrei, A. carolinensis and A. valencienni), representing three different ecomorphs (trunk-ground, trunk-crown, and twig, respectively). We did so by measuring maximal acceleration capacity of the three species on a broad and narrow dowel. In addition to acceleration capacity, we quantified maximal sprint speed on both dowels. Both acceleration capacity and sprint speed are affected by substrate diameter, but the way in which they are, differs among species. Acceleration capacity in the trunk-ground anole, A. sagrei,was least affected by dowel diameter, whereas it was greatly reduced on the narrow dowel in the twig anole, A. valencienni. Sprint speed on the narrow dowel, however, was reduced to the greatest extent in the fastest running species, A. sagrei, whereas sprint speed was hardly affected by dowel diameter in the slow A. valencienni. The differential effect of dowel diameter on maximal acceleration capacity cannot be explained by differences in the timing of reaching maximal acceleration, but may be due to interspecific differences in the relative positioning of the limbs on the different dowels. The differential effect of dowel diameter on sprint speed,on the other hand, may be based on interspecific differences in the relative contribution of subsequent acceleratory bouts to maximal sprint speed on the broad and narrow dowel.
Electrical and Mechanical Properties of Conducive Carbon Black/Polyolefin Composites Mixed With Carbon Fiber
Authors: Farshidfar A , Haddadi-Asl V , Nazokdast H 
Published: November 2006

Abstract
The electrical conductivity of polymers can be increased by the addition of conductive fillers, including forms of carbon fibers and carbon black. The resulting composites can be used in applications where metals have typically been the materials of choice. The advantages of using these materials include lighter weight, resistance to corrosion, and the ability to be readily adapted to the needs of a specific application. One of the most significant applications for conductive polymer composites are conductive carbon-polymer composite electrodes. As many properties such as conductivity, mechanical integrity, low permeability, electrochemical activity, and stability in the electrolytes are required of materials to be used as electrodes, so “material selection” plays a crucial role in fabricating these materials. In this work it was found that high density polyethylene (HDPE)/ethylene-propylene-diene monomer(EPDM) blend ratio (70/30) has lower percolation threshold and volume resistivity than individually carbon black filled HDPE and EPDM due to “double percolation” effect. Carbon fibers were also added to the polymer-carbon black mixtures to enhance the conductivity and mechanical properties. The electrical conductivity of composites with different ratios of carbon black (CB) content to carbon fiber (CF) content was studied. The CB content is the main factor to determine the resistivity of the composites filled with CB and CF. Mechanical properties, including tensile strength, elongation at break, and impact strength of the conductive composites were evaluated. The results showed that incorporation of CB and CF in the composites will enhance tensile strength, but decrease elongation at break and impact strength of the composites. In mechanical properties, CF content has a greater effect than CB content. From the comparison of the resistivity and mechanical properties of the composites filled with CB and CF with that of the composites filled with CB only, it is concluded that using CF as a substitute for part of the CB in CB-filled composites can enhance electrical and mechanical properties.