bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte Chemoattractant Protein‐1 Plays a Dominant Role in the Chronic Inflammation Observed in Alzheimer's Disease
Authors: Sokolova Anna , Hill Michelle D. , Rahimi Farid , Warden Lolita A. , Halliday Glenda M. , Shepherd Claire E. 
Published: July 2008

AbstractChronic neuroinflammation correlates with cognitive decline and brain atrophy in Alzheimer's disease (AD), and cytokines and chemokines mediate the inflammatory response. However, quantitation of cytokines and chemokines in AD brain tissue has only been carried out for a small number of mediators with variable results. We simultaneously quantified 17 cytokines and chemokines in brain tissue extracts from controls (n = 10) and from patients with and without genetic forms of AD (n = 12). Group comparisons accounting for multiple testing revealed that monocyte chemoattractant protein‐1 (MCP‐1), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) were consistently upregulated in AD brain tissue. Immunohistochemistry for MCP‐1, IL‐6 and IL‐8 confirmed this increase and determined localization of these factors in neurons (MCP‐1, IL‐6, IL‐8), astrocytes (MCP‐1, IL‐6) and plaque pathology (MCP‐1, IL‐8). Logistic linear regression modeling determined that MCP‐1 was the most reliable predictor of disease. Our data support previous work on significant increases in IL‐6 and IL‐8 in AD but indicate that MCP‐1 may play a more dominant role in chronic inflammation in AD.
Modified Reynolds Equation for Aerostatic Porous Radial Bearings With Quadratic Forchheimer Pressure-Flow Assumption
Authors: Nicoletti Rodrigo , Silveira Zilda C. , Purquerio Benedito M. 
Published: July 2008

Abstract
Aerostatic porous bearings are becoming important elements in precision machines due to their inherent characteristics. The mathematical modeling of such bearings depends on the pressure-flow assumptions that are adopted for the flow in the porous medium. In this work, one proposes a nondimensional modified Reynolds equations based on the quadratic Forchheimer assumption. In this quadratic approach, the nondimensional parameter Φ strongly affects the bearing load capacity, by defining the nonlinearity level of the system. For values of Φ&gt;10, the results obtained with the modified Reynolds equation with quadratic Forchheimer assumption tend to those obtained with the linear Darcy model, thus showing that this is a more robust and global approach of the problem, and can be used for both pressure-flow assumptions (linear and quadratic). The threshold between linear and quadratic assumptions is numerically investigated for a bronze sintered porous bearing, and the effects of bearing geometry are discussed. Numerical results show that Φ strongly affects the bearing loading capacity and stiffness coefficients.
Neisseria meningitidisPorB, a Toll-Like Receptor 2 Ligand, Improves the Capacity ofFrancisella tularensisLipopolysaccharide To Protect Mice against Experimental Tularemia
Authors: Chiavolini Damiana , Weir Susan , Murphy John R. , Wetzler Lee M. 
Published: July 2008

ABSTRACTFrancisella tularensiscauses severe pneumonia that can be fatal if it is left untreated. Due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. PorB, a porin fromNeisseria meningitidis, is a well-established Toll-like receptor 2 ligand and has been shown to be a promising vaccine adjuvant candidate due to its ability to enhance the T-cell costimulatory activity of antigen-presenting cells both in vitro and in vivo. BALB/c mice were immunized with lipopolysaccharide (LPS) isolated from theF. tularensissubsp.holarcticalive vaccine strain (LVS), with or without PorB fromN. meningitidis, and the antibody levels induced during the vaccination regimen and the level of protection against intranasal challenge with LVS were determined. Antigen administered alone induced a specificF. tularensisLPS immunoglobulin M (IgM) response that was not maintained over the weeks and that conferred protection to only 25% of the mice. In contrast,F. tularensisLPS given in combination with neisserial PorB induced consistent levels of specific IgM throughout the immunization and increased the proportion of surviving mice to 70%. Postchallenge cytokine analysis showed that interleukin-6 (IL-6), monocyte chemoattractant protein 1, and gamma interferon were markers of mortality and that IL-1β was a correlate of survival, independent of the presence of PorB as an adjuvant. These data indicate that neisserial PorB might be an optimal candidate adjuvant for improving the protective effect ofF. tularensisLPS and other subunit vaccines against tularemia, but there is still a need to test its efficacy against virulent type A and type BF. tularensisstrains.
Prevalence of Human Parechovirus in The Netherlands in 2000 to 2007
Authors: van der Sanden Sabine , de Bruin Erwin , Vennema Harry , Swanink Caroline , Koopmans Marion , van der Avoort Harrie 
Published: July 2008

ABSTRACT
Infection with human parechovirus 3 (HPeV3) was described for the first time in Japan in 2004 and reportedly is more often associated with severe disease than infection with HPeV1 or HPeV2. In 2004, infections with HPeV3 were observed for the first time in The Netherlands. Genetic analysis showed several different lineages, suggesting endemic circulation. We analyzed 163 cell culture isolates from the same number of patients tested in routine virological laboratories as part of the national enterovirus surveillance program. Isolates were collected between 2000 and 2007 and could not be characterized by routine methods. In total, 155 isolates (95%) were found positive for HPeV by a reverse transcription-PCR assay targeting the 5′ untranslated region, explaining the majority of the diagnostic deficit in enterovirus surveillance for these years. Typing of the isolates by use of partial genome sequencing of the VP1/2A region revealed the presence of 55 HPeV1, 2 HPeV2, 89 HPeV3, 1 HPeV4, and 8 HPeV5 isolates. We compared isolation dates, age groups affected, and clinical pictures, which were reported as part of the routine surveillance. Clear differences in epidemiology were observed, with HPeV3 occurring at intervals of 2 years and in the spring-summer season, whereas HPeV1 was observed in small numbers throughout each year, with a low in the summer months. HPeV3 infection affected younger children than HPeV1 infection and was significantly more often associated with fever, meningitis, and viremia.
Pharmacoeconomic Analysis of Microbiologic Techniques for Differentiating Staphylococci Directly from Blood Culture Bottles
Authors: Hermsen Elizabeth D. , Shull Sara S. , Klepser Donald G. , Iwen Peter C. , Armbrust Amy , Garrett Jodi , Freifeld Alison G. , Rupp Mark E. 
Published: July 2008

ABSTRACT

Differentiating staphylococci in blood cultures is a critical issue, particularly when only one of two cultures is positive by Gram staining for staphylococci. New tests for the identification of
Staphylococcus aureus
allow faster results and definitive treatment compared to the tube coagulase test interpreted at 24 h (TCT24). These newer tests, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) and real-time PCR (RT-PCR), offer improved sensitivity at higher cost. Data suggest that the tube coagulase test may be interpreted at 4 h (TCT4) with little loss of sensitivity. The impact of variability in turnaround time, sensitivity, specificity, and cost on comparative cost-effectiveness is unknown. Our aim was to establish the cost-effectiveness of TCT24, PNA-FISH, RT-PCR, and TCT4 for direct identification of staphylococci in blood cultures. Decision analysis comparing these strategies was done from the institutional perspective. Besides test variables, other variables included patient risk factors, empirical treatment, and follow-up cultures. Probability and cost estimates came from the literature and institutional data. Base case estimates were derived from institutional rates of 73% contamination when coagulase-negative staphylococci were identified, 67.6% prevalence of risk factors, and 12.4% prevalence of
S. aureus
when one of two cultures yielded staphylococci. Sensitivity analysis was done across a range of probabilities and costs. In the base case, TCT4 and TCT24 were more cost-effective than RT-PCR and PNA-FISH ($78 versus $120 versus $165 per patient, respectively). The advantage of TCT4 and TCT24 remained robust upon sensitivity analysis. TCT4 should be further evaluated as a rapid, cost-effective means for identification of
S. aureus
in blood cultures.
Viability of
Trichomonas vaginalis
in Copan Universal Transport Medium and eSwab Transport Medium
Authors: Rivers C. A. , Schwebke J. R. 
Published: July 2008

ABSTRACT

We compared the use of universal transport medium and eSwab transport medium held at room temperature or 37°C to bedside inoculation and immediate incubation of culture media for the detection of
Trichomonas vaginalis
. There were no significant culturable differences in the sensitivity of either of the transport media to that of bedside inoculation.
Internally Controlled Triplex Quantitative PCR Assay for Human Polyomaviruses JC and BK
Authors: Dumonceaux Timothy J. , Mesa Christine , Severini Alberto 
Published: July 2008

ABSTRACT

We have developed a triplex TaqMan-based quantitative PCR assay for the human polyomaviruses JC (JCPyV) and BK (BKPyV). The assay simultaneously detects and quantifies both JCPyV and BKPyV in human clinical samples, and it includes an internal amplification control consisting of murine polyomavirus (MuPyV) plasmid DNA. We developed the assay for the Roche LightCycler 480 platform with the reporter dyes VIC, 6-FAM, and Cy5 for MuPyV, BKPyV, and JCPyV, respectively. The assay had a high specificity for BKPyV and JCPyV when either viral genome was present alone or in mixed samples over a range of 10
1
to 10
7
copy numbers per reaction. The analytical sensitivity was 50 copies for BKPyV and 10 copies for JCPyV. The use of the MuPyV internal control ensured monitoring of the quality of the extraction and of PCR inhibition, even in samples such as cerebrospinal fluid and plasma in which controls based on host genes cannot be effectively used. In addition, we developed a similar assay using a different dye configuration (6-FAM, VIC, and NED) that could be used on an ABI 7500 Fast platform. This assay had sensitivities similar to those of the LightCycler 480 configuration for BKPyV and JCPyV when either viral genome was present alone, but the sensitivity of detection of BKPyV was greatly decreased when an excess of JCPyV (>100-fold) was present in the sample. This internally controlled combined assay offers greater convenience and cost-effectiveness compared to separate assays for each virus and can also detect unexpected PyV activations by testing for both viruses in all samples.
Novel Genospecies of
Borrelia burgdorferi
Sensu Lato from Rodents and Ticks in Southwestern China
Authors: Chu Chen-Yi , Liu Wei , Jiang Bao-Gui , Wang Ding-Ming , Jiang Wei-Jia , Zhao Qiu-Min , Zhang Pan-He , Wang Zhao-Xiao , Tang Guang-Peng , Yang Hong , Cao Wu-Chun 
Published: July 2008

ABSTRACT

By using multilocus sequence analysis, five
Borrelia valaisiana
-related strains isolated from rodents and ticks in southwestern China were eventually classified as a new genospecies of
B. burgdorferi
sensu lato rather than
B. valaisiana
. The finding explained the differences in transmission cycle and phenotype between
B. valaisiana
strains from Europe and
B. valaisiana
-related strains from eastern Asia.
MVPlex Assay for Direct Detection of Methicillin-Resistant
Staphylococcus aureus
in Naris and Other Swab Specimens
Authors: Podzorski Raymond P. , Li Haijing , Han Jian , Tang Yi-Wei 
Published: July 2008

ABSTRACT

We evaluated the MVPlex assay (Geneco Biomedical Products), which uses target-enriched multiplex PCR amplification followed by liquid array identification, for the detection of methicillin-resistant
Staphylococcus aureus
(MRSA) from 307 dual-swab specimens. By using a combination of culture (Trypticase soy agar-5% sheep blood agar and Columbia CNA agar-5% sheep blood) and an FDA-approved MRSA PCR assay as the “gold standard,” the MVPlex MRSA assay and culture were found to have sensitivities of 97.8% and 84.4% (
P
= 0.002) and specificities of 95.8% and 98.6% (
P
< 0.05), respectively.
Importance of NKT Cells in Resistance to Herpes Simplex Virus, Fate of Virus-Infected Neurons, and Level of Latency in Mice
Authors: Grubor-Bauk Branka , Arthur Jane Louise , Mayrhofer Graham 
Published: July 2008

ABSTRACTHerpes simplex virus type 1 (HSV-1) produces acute mucocutaneous infections, spread to sensory ganglia, and establishment of latency. In addition, neurovirulent strains have potential to invade the central nervous system (CNS), with potentially a lethal outcome. Early activation of defenses at all stages is essential to limit virus load and reduce the risk of neuronal damage, extensive zosteriform skin lesions, and catastrophic spread to the CNS. NKT cells respond rapidly, and we have shown previously that CD1d-deficient mice are compromised in controlling a neuroinvasive isolate of HSV-1. We now compare infection in Jα18 GKO and CD1d GKO mice, allowing direct assessment of the importance of invariant Vα14+NKT cells and deduction of the role of the CD1d-restricted NKT cells with diverse T-cell receptors. The results indicate that both subsets of NKT cells contribute to virus control both in the afferent phase of infection and in determining the mortality, neuroinvasion, loss of sensory neurons, size of zosteriform, lesions and levels of latency. In particular, both are crucial determinants of clinical outcome, providing protection equivalent to a 1-log dose of virus. These NKT cells can be expected to provide protection at doses of virus that might be encountered naturally.
A Single Amino Acid Residue Change in the P Protein of Parainfluenza Virus 5 Elevates Viral Gene Expression
Authors: Timani Khalid A. , Sun Dengyun , Sun Minghao , Keim Celia , Lin Yuan , Schmitt Phuong Tieu , Schmitt Anthony P. , He Biao 
Published: July 2008

ABSTRACT

Parainfluenza virus 5 (PIV5) is a prototypical paramyxovirus. The V/P gene of PIV5 encodes two mRNA species through a process of pseudotemplated insertion of two G residues at a specific site during transcription, resulting in two viral proteins, V and P, whose N termini of 164 amino acid residues are identical. Previously it was reported that mutating six amino acid residues within this identical region results in a recombinant PIV5 (rPIV5-CPI−) that exhibits elevated viral protein expression and induces production of cytokines, such as beta interferon and interleukin 6. Because the six mutations correspond to the shared region of the V protein and the P protein, it is not clear whether the phenotypes associated with rPIV5-CPI− are due to mutations in the P protein and/or mutations in the V protein. To address this question, we used a minigenome system and recombinant viruses to study the effects of mutations on the functions of the P and V proteins. We found that the P protein with six amino acid residue changes (Pcpi−) was more efficient than wild-type P in facilitating replication of viral RNA, while the V protein with six amino acid residue changes (Vcpi−) still inhibits minigenome replication as does the wild-type V protein. These results indicate that elevated viral gene expression in rPIV5-CPI− virus-infected cells can be attributed to a P protein with an increased ability to facilitate viral RNA synthesis. Furthermore, we found that a single amino acid residue change at position 157 of the P protein from Ser (the residue in the wild-type P protein) to Phe (the residue in Pcpi−) is sufficient for elevated viral gene expression. Using mass spectrometry and
33
P labeling, we found that residue S157 of the P protein is phosphorylated. Based on these results, we propose that phosphorylation of the P protein at residue 157 plays an important role in regulating viral RNA replication.
Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains
Authors: Adams A. Paige , Aronson Judith F. , Tardif Suzette D. , Patterson Jean L. , Brasky Kathleen M. , Geiger Robert , de la Garza Melissa , Carrion Ricardo , Weaver Scott C. 
Published: July 2008

ABSTRACTEastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log10PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.
Immune Response in the Absence of Neurovirulence in Mice Infected with M Protein Mutant Vesicular Stomatitis Virus
Authors: Ahmed Maryam , Marino Tracie R. , Puckett Shelby , Kock Nancy D. , Lyles Douglas S. 
Published: July 2008

ABSTRACT
Matrix (M) protein mutants of vesicular stomatitis virus (VSV), such as rM51R-M virus, are less virulent than wild-type (wt) VSV strains due to their inability to suppress innate immunity. Studies presented here show that when inoculated intranasally into mice, rM51R-M virus was cleared from nasal mucosa by day 2 postinfection and was attenuated for spread to the central nervous system, in contrast to wt VSV, thus accounting for its reduced virulence. However, it stimulated an antibody response similar to that in mice infected with the wt virus, indicating that it has the ability to induce adaptive immunity in vivo without causing disease. These results support the use of M protein mutants of VSV as vaccine vectors.
Distinct Requirements of Adenovirus E1b55K Protein for Degradation of Cellular Substrates
Authors: Schwartz Rachel A. , Lakdawala Seema S. , Eshleman Heather D. , Russell Matthew R. , Carson Christian T. , Weitzman Matthew D. 
Published: July 2008

ABSTRACT
The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex together with cellular proteins including cullin 5, elongins B and C, and Rbx1. This complex possesses E3 ubiquitin ligase activity and targets cellular proteins for proteasome-mediated degradation. The ligase activity has been suggested to be responsible for all functions of E1b55K/E4orf6, including promoting efficient viral DNA replication, preventing a cellular DNA damage response, and stimulating late viral mRNA nuclear export and late protein synthesis. The known cellular substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the degradation of individual targets can occur independently of other substrates. Furthermore, we identify separation-of-function mutant forms of E1b55K that can distinguish substrates for binding and degradation. Our results identify distinct regions of E1b55K that are involved in substrate recognition but also imply that there are additional requirements beyond protein association. These mutant proteins will facilitate the determination of the relevance of specific substrates to the functions of E1b55K in promoting infection and inactivating host defenses.
Presence of the Adenovirus IVa2 Protein at a Single Vertex of the Mature Virion
Authors: Christensen Joan B. , Byrd Serena A. , Walker Angela K. , Strahler John R. , Andrews Philip C. , Imperiale Michael J. 
Published: July 2008

ABSTRACT
Assembly of adenovirus particles is thought to be similar to that of bacteriophages, in which the double-stranded DNA genome is inserted into a preformed empty capsid. Previous studies from our and other laboratories have implicated the viral IVa2 protein as a key component of the encapsidation process. IVa2 binds to the packaging sequence on the viral chromosome in a sequence-specific manner, alone and in conjunction with the viral L4 22K protein. In addition, it interacts with the viral L1 52/55-kDa protein, which is required for DNA packaging. Finally, a mutant virus that does not produce IVa2 is unable to produce any capsids. Therefore, it has been proposed that IVa2 nucleates capsid assembly. A prediction of such a model is that the IVa2 protein would be found at a unique vertex of the mature virion. In this study, the location of IVa2 in the virion has been analyzed using immunogold staining and electron microscopy, and the copy number of IVa2 in virions was determined using three independent methods, quantitative mass spectrometry, metabolic labeling, and Western blotting. The results indicate that it resides at a unique vertex and that there are approximately six to eight IVa2 molecules in each particle. These findings support the hypothesis that the IVa2 protein plays multiple roles in the viral assembly process.