bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of cellular redox status by stable isotope dilution liquid chromatography/mass spectrometry analysis of glutathione and glutathione disulfide
Authors: Zhu Peijuan , Oe Tomoyuki , Blair Ian A. 
Published: January 2008

AbstractOxidation of glutathione (GSH) to glutathione disulfide (GSSG) occurs during cellular oxidative stress. The redox potential of the 2GSH/GSSG couple, which is determined by the Nernst equation, provides a means to assess cellular redox status. It is difficult to accurately quantify GSH and GSSG due to the ease with which GSH is oxidized to GSSG during sample preparation. To overcome this problem, a stable isotope dilution liquid chromatography/multiple reaction monitoring mass spectrometry (LC/MRM‐MS) method has been developed using 4‐fluoro‐7‐sulfamoylbenzofurazan (ABD‐F) derivatization. ABD‐F derivatization of the GSH thiol group was rapid, quantitative, and occurred at room temperature. The LC/MRM‐MS method, which requires no sample clean‐up, was validated within the calibration ranges of 5 to 400 nmol/mL in cell lysates for GSH and 0.5 to 40 nmol/mL in cell lysates for GSSG. Calibration curves prepared by adding known concentrations of GSH and GSSG to cell lysates were parallel to the standard curve prepared in buffers. GSH and GSSG concentrations were determined in two monocyte/macrophage RAW 267.4 cell lines with or without 15‐LOX‐1 expression (R15LO and RMock cells, respectively) after treatment with the bifunctional electrophile 4‐oxo‐2(E)‐nonenal (ONE). R15LO cells synthesized much higher concentrations of the lipid hydroperoxide, 15(S)‐hydroperoxyeicosatetraenoic acid (15‐HPETE), which undergoes homolytic decomposition to ONE. GSH was depleted by ONE treatment in both RMock and R15LO cells, leading to significant increases in their redox potentials. However, R15LO cells had higher GSH concentrations (most likely through increased GSH biosynthesis) and had increased resistance to ONE‐mediated GSH depletion than RMock cells. Consequently, R15LO cells had lower reduction potentials at all concentrations of ONE. GSSG concentrations were higher in R15LO cells after ONE treatment when compared with the ONE‐treated RMock cells. This suggests that increased expression of 15(S)‐HPETE modulates the activity of cellular GSH reductases or the transporters involved in removal of GSSG. Copyright © 2008 John Wiley & Sons, Ltd.
An electrospray mass spectrometric method for accurate mass determination of highly acid‐sensitive phosphoramidites
Authors: Kupihár Zoltán , Timár Zoltán , Darula Zsuzsanna , Dellinger Douglas J. , Caruthers Marvin H. 
Published: January 2008

AbstractAn accurate mass determination method utilizing electrospray ionization mass spectrometry is described for analysis of several different types of phosphoramidites that are extremely acid‐sensitive compounds. An earlier method, which applied a LiCl/acetonitrile system, was extended for this special application by using polymeric standards including poly(ethylene glycol) (PEG), poly(ethylene glycol) dimethyl ether (PDE) and poly(propylene glycol) (PPG). Concentrations of standards, samples and LiCl were optimized and potential impurities that affect the analyses were also investigated. Copyright © 2008 John Wiley & Sons, Ltd.
Baptism of ice: J. G. Bartholomew and the naming of Antarctica
Authors: Mawer G.A. 
Published: January 2008

ABSTRACTAs a proper noun, Antarctica has a long pedigree but a short history. It was coined and popularised by the Edinburgh mapmaker J. G. Bartholomew in the 1890s as a label for the supposed south polar continent outlined by John Murray of the Challenger Commission. By 1902 it was ‘slowly coming into use’ and by 1928 had been ‘generally received’ by geographers.
Defining products for a new health technology assessment agency in Madrid, Spain: A survey of decision makers
Authors: Andradas Elena , Blasco Juan-Antonio , Valentín Beatriz , López-Pedraza María-José , Gracia Francisco-Javier 
Published: January 2008

Objectives:The aim of this study was to explore the needs and requirements of decision makers in our regional healthcare system for health technology assessment (HTA) products to support portfolio development planning for a new HTA agency in Madrid, Spain.Methods:A Delphi study was conducted during 2003. Questionnaires were developed based on a review of products and services offered by other agency members of the International Network of Agencies for Health Technology Assessment, and included preference and prioritization questions to evaluate twenty-two different products and services. The initial Delphi panel involved eighty-seven experts from twenty-one public hospitals, eleven primary healthcare centers, six private hospitals, and eight departments of the Regional Ministry of Health of the Community of Madrid.Results:The global participation rate was 83.9 percent. Ten of the twenty-two possible products were rated of high interest by more than 80 percent of respondents. Important differences in preferences and priorities were detected across different settings. Public hospitals and primary healthcare centers shared a more “micro” perspective, preferring classic technology-centered HTA products, whereas private hospitals and Ministry representatives demanded more “macro” products and services such as organizational model and information system assessments.Conclusions:The high participation rate supports the representativeness of the results for our regional context. The strategic development of an HTA portfolio based on decision makers’ needs and requirements as identified in this type of exercise should help achieve a better impact on policy development and decision making.
Measuring the validity of early health technology assessment: Bibliometrics as a tool to indicate its scientific basis
Authors: Lundberg Jonas , Brommels Mats , Skår John , Tomson Göran 
Published: January 2008

Objectives:The aim of this study was to assess whether publications of importance for improving the health system and its technologies are highly cited intrascientifically.Methods:Bibliometric assessment of the 596 publications used as sources in the fifty SBU Alerts from 2001to 2004 from the Swedish Council on Technology Assessment in Health Care was carried out using the Thomson Scientific citation indexes. Normalized citation scores were calculated for all included studies. Additional factors such as the time and place of the research, subject categories, and journal source were analyzed.Results:On average, the sources in SBU Alert have been cited eight times more than the world average consistently during the time period and across research areas. Articles used as its scientific basis are often published in a few, high impact, general medical journals. However, many of the articles are published in field-specific journals with low impact factors. Most articles used in SBU Alert are published by authors based in the United States or the United Kingdom. However, Swedish, Danish, and Dutch publications are overrepresented in its science base, whereas Japanese, Taiwanese, Indian, and Russian publications are underrepresented.Conclusions:Publications used as sources in a Swedish system for identification and early assessment of new methods in health care are also highly cited within the scientific community. This finding increases the appropriateness of using bibliometric indicators in evaluations of clinical research and suggests that decision makers through SBU Alert are getting scientifically sound advice.
Does income influence demand for medical services despite Japan's “Health Care for All” policy?
Authors: Babazono Akira , Kuwabara Kazuaki , Hagihara Akito , Yamamoto Eiji , Hillman Alan 
Published: January 2008

Objectives:We examined the impact of household income on the use of medical services in Japan, where there is a “health care for all” policy, with important, centralized influence by the national government designed to ensure universal access.Methods and Subjects:All healthcare societies operating in 2003 were included in the study, representing 14,776,193 insured adults and 15,496,752 insured dependents. The mean case rate (the average number of monthly bills per patient), the mean number of service days per person, and the mean medical cost per person served as indicators of medical service use. Multiple regression analysis was performed by the forced entry method using case rate, the number of service days, and medical cost as outcome variables, and average monthly salary, dependent ratio, average age, and premium rate as the explanatory variables.Results:In the multiple regression analyses, average monthly salary showed a high positive correlation of outpatient and dental indicators, including case rate, the number of service days, and medical cost. If the average monthly salary were reduced 20 percent lower than the mean, the estimated changes (95 percent CI) in case rate for the insured were −7.49 (−8.14 ∼ −6.84) percent for outpatient visits and −8.16 (−8.77 ∼ −7.56) percent for dental services.Conclusions:Average monthly salary intensifies the effects of copayments on the case rate, the number of service days, and medical cost in the “Employees Health Insurance” in Japan. Thus, a low salary appears to discourage patients from seeking medical and dental services.
Mannheimia haemolyticaand bovine respiratory disease
Authors: Rice J. A. , Carrasco-Medina L. , Hodgins D. C. , Shewen P. E. 
Published: January 2008

AbstractMannheimia haemolyticais the principal bacterium isolated from respiratory disease in feedlot cattle and is a significant component of enzootic pneumonia in all neonatal calves. A commensal of the nasopharynx,M. haemolyticais an opportunist, gaining access to the lungs when host defenses are compromised by stress or infection with respiratory viruses or mycoplasma. Although several serotypes act as commensals, A1 and A6 are the most frequent isolates from pneumonic lungs. Potential virulence factors include adhesin, capsular polysaccharide, fimbriae, iron-regulated outer membrane proteins, leukotoxin (Lkt), lipopolysaccharide (LPS), lipoproteins, neuraminidase, sialoglycoprotease and transferrin-binding proteins. Of these, Lkt is pivotal in induction of pneumonia. Lkt-mediated infiltration and destruction of neutrophils and other leukocytes impairs bacterial clearance and contributes to development of fibrinous pneumonia. LPS may act synergistically with Lkt, enhancing its effects and contributing endotoxic activity. Antibiotics are employed extensively in the feedlot industry, both prophylactically and therapeutically, but their efficacy varies because of inconsistencies in diagnosis and treatment regimes and development of antibiotic resistance. Vaccines have been used for many decades, even though traditional bacterins failed to demonstrate protection and their use often enhanced disease in vaccinated animals. Modern vaccines use culture supernatants containing Lkt and other soluble antigens, or bacterial extracts, alone or combined with bacterins. These vaccines have 50–70% efficacy in prevention ofM. haemolyticapneumonia. Effective control ofM. haemolyticapneumonia is likely to require a combination of more definitive diagnosis, efficacious vaccines, therapeutic intervention and improved management practices.
Precise score for the prediction of peptides cleaved by the proteasome
Authors: Ginodi Ido , Vider-Shalit Tal , Tsaban Lea , Louzoun Yoram 
Published: January 2008

Abstract
Motivation: An 8–10mer can become a cytotoxic T lymphocyte epitope only if it is cleaved by the proteasome, transported by TAP and presented by MHC-I molecules. Thus most of the epitopes presented to cytotoxic T cells in the context of MHC-I molecules are products of intracellular proteasomal cleavage. These products are not random, as peptide production is a function of the precise sequence of the proteins processed by the proteasome.
Results: We have developed a score for the probability that a given peptide results from proteasomal cleavage. High scoring peptides are those that are cleaved in their extremities and not in their center, while low scoring peptides are either cleaved in their centers or not cleaved in their extremities. The current work differs from most previous works, in that it determines the production probability of an entire peptide, rather than trying to predict specific cleavage sites. We further present different score functions for the constitutive and the immunoproteasome. Our results were validated to have low error levels against multiple epitope databases. We provide here a novel computational tool and a website to use it—http://peptibase.cs.biu.ac.il/PepCleave_II/ to assess the probability that a given peptide indeed results from proteasomal cleavage.
Contact: louzouy@math.biu.ac.il
Supplementary information: Supplementary data are available at Bioinformatics online.
Observation of multiple folding pathways of β-hairpin trpzip2 from independent continuous folding trajectories
Authors: Chen Changjun , Xiao Yi 
Published: January 2008

Abstract
Motivation: After 10-year investigations, the folding mechanisms of β-hairpins are still under debate. Experiments strongly support zip-out pathway, while most simulations prefer the hydrophobic collapse model (including middle-out and zip-in pathways). In this article, we show that all pathways can occur during the folding of β-hairpins but with different probabilities. The zip-out pathway is the most probable one. This is in agreement with the experimental results. We came to our conclusions by 38 100-ns room-temperature all-atom molecular dynamics simulations of the β-hairpin trpzip2. Our results may help to clarify the inconsistencies in the current pictures of β-hairpin folding mechanisms.
Contact: yxiao@mail.hust.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Keeping up with a warming world; assessing the rate of adaptation to climate change
Authors: Visser Marcel E 
Published: January 2008

The pivotal question in the debate on the ecological effects of climate change is whether species will be able to adapt fast enough to keep up with their changing environment. If we establish the maximal rate of adaptation, this will set an upper limit to the rate at which temperatures can increase without loss of biodiversity.The rate of adaptation will primarily be set by the rate of microevolution since (i) phenotypic plasticity alone is not sufficient as reaction norms will no longer be adaptive and hence microevolution on the reaction norm is needed, (ii) learning will be favourable to the individual but cannot be passed on to the next generations, (iii) maternal effects may play a role but, as with other forms of phenotypic plasticity, the response of offspring to the maternal cues will no longer be adaptive in a changing environment, and (iv) adaptation via immigration of individuals with genotypes adapted to warmer environments also involves microevolution as these genotypes are better adapted in terms of temperature, but not in terms of, for instance, photoperiod.Long-term studies on wild populations with individually known animals play an essential role in detecting and understanding the temporal trends in life-history traits, and to estimate the heritability of, and selection pressures on, life-history traits. However, additional measurements on other trophic levels and on the mechanisms underlying phenotypic plasticity are needed to predict the rate of microevolution, especially under changing conditions.Using this knowledge on heritability of, and selection on, life-history traits, in combination with climate scenarios, we will be able to predict the rate of adaptation for different climate scenarios. The final step is to use ecoevolutionary dynamical models to make the link to population viability and from there to biodiversity loss for those scenarios where the rate of adaptation is insufficient.
Cytomegalovirus Strain Diversity in Seropositive Women
Authors: Novak Zdenek , Ross Shannon A. , Patro Raj Kumar , Pati Sunil Kumar , Kumbla Rekha A. , Brice Sallie , Boppana Suresh B. 
Published: January 2008

ABSTRACT
Infection and reinfection with multiple cytomegalovirus (CMV) strains have been shown to occur in immunocompromised individuals, sexually transmitted disease clinic attendees, and children attending day care centers. To characterize the CMV diversity in healthy seropositive individuals, 16 CMV PCR-positive specimens from 113 seropositive women were analyzed for glycoprotein gN and gB genotypes by cloning, followed by nucleotide sequencing of the plasmid DNA and/or restriction fragment length polymorphism (RFLP). The results showed that most (93.7%) of the PCR-positive specimens contained multiple gN and/or gB genomic variants, suggesting that the majority of women were infected with more than one virus strain. The results also showed that the RFLP technique might not be sufficiently sensitive to detect all of the genomic variants present in a sample.
Genotype-Specific Genomic Markers Associated with Primary Hepatomas, Based on Complete Genomic Sequencing of Hepatitis B Virus
Authors: Sung Joseph J. Y. , Tsui Stephen K. W. , Tse Chi-Hang , Ng Eddie Y. T. , Leung Kwong-Sak , Lee Kin-Hong , Mok Tony S. K. , Bartholomeusz Angeline , Au Thomas C. C. , Tsoi Kelvin K. F. , Locarnini Stephen , Chan Henry L. Y. 
Published: January 2008

ABSTRACT
We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome. Data mining and rule learning were employed to develop diagnostic algorithms. An independent cohort of 132 cases (43 HCC and 89 non-HCC) was used to validate the accuracy of these algorithms. Among the 100 cases of HCC, 37 had genotype B (all subgenotype Ba) and 63 had genotype C (16 subgenotype Ce and 47 subgenotype Cs) HBV infection. In the control group, 51 had genotype B and 49 had genotype C (10 subgenotype Ce and 39 subgenotype Cs) HBV infection. Genomic algorithms associated with HCC were derived based on genotype/subgenotype-specific mutations. In genotype B HBV, mutations C1165T, A1762T and G1764A, T2712C/A/G, and A/T2525C were associated with HCC. HCC-related mutations T31C, T53C, and A1499G were associated with HBV subgenotype Ce, and mutations G1613A, G1899A, T2170C/G, and T2441C were associated with HBV subgenotype Cs. Amino acid changes caused by these mutations were found in the X, envelope, and precore/core regions in association with HBV genotype B, Ce, and Cs, respectively. In conclusion, infections with different genotypes of HBV (B, Ce, and Cs) carry different genomic markers for HCC at different parts of the HBV genome. Different HBV genotypes may have different virologic mechanisms of hepatocarcinogenesis.
Analysis of the Evolutionary Forces in an Immunodominant CD8 Epitope in Hepatitis C Virus at a Population Level
Authors: Neumann-Haefelin Christoph , Frick David N. , Wang Jing Jing , Pybus Oliver G. , Salloum Shadi , Narula Gagandeep S. , Eckart Anna , Biezynski Andrea , Eiermann Thomas , Klenerman Paul , Viazov Sergei , Roggendorf Michael , Thimme Robert , Reiser Markus , Timm Jörg 
Published: January 2008

ABSTRACTFailure of the adaptive immune response to control infection with the hepatitis C virus (HCV) can result from mutational escape in targeted T-cell epitopes. Recent studies suggest that T-cell immune pressure is an important factor in the evolution of the nonstructural proteins in HCV. The aim of this study was to characterize the forces that contribute to viral evolution in an HLA-A*01-restricted epitope in HCV NS3. This epitope represents a potentially attractive target for vaccination strategies since it is conserved across all genotypes. In our cohort of subjects with chronic HCV infection (genotype 1b or 3a), it is a frequently recognized CD8 epitope in HLA-A*01-positive subjects. Viral sequence data reveal that an escape variant is the dominant residue in both genotypes. The predominant Y1444F substitution seemingly impairs binding to the HLA-A*01 molecule, which may have an important impact on the ability to prime a functional CD8 response upon infection. Interestingly, a case of evolution toward the prototype sequence was observed during chronic infection, possibly because the helicase activity of the protein containing the Y1444F substitution is reduced compared to the prototype sequence. Comparison of HCV sequences from Asia and Europe suggests that the frequency of the HLA-A*01 allele in a population may influence the frequency of the escape variant in circulating strains. These data suggest a complex interaction of multiple forces shaping the evolution of HCV in which immune pressure both within the individual and also at the population level in addition to functional constraints are important contributing factors.
The Full-Length Protein Encoded by Human Cytomegalovirus Gene UL117 Is Required for the Proper Maturation of Viral Replication Compartments
Authors: Qian Zhikang , Xuan Baoqin , Hong Te Tee , Yu Dong 
Published: January 2008

ABSTRACT
Previously, two large-scale mutagenic analyses showed that mutations in the human cytomegalovirus (HCMV) gene UL117 resulted in a defect in virus growth in fibroblasts. Early transcriptional analyses have revealed several mRNAs from the UL119-UL115 region; however, specific transcripts encoding UL117-related proteins have not been identified. In this study, we identified two novel transcripts arising from the UL117 gene locus, and we reported that the UL117 open reading frame encoded the full-length protein pUL117 (45 kDa) and the shorter isoform pUL117.5 (35 kDa) as the result of translation initiation at alternative in-frame ATGs. Both proteins were expressed with early kinetics, but pUL117 accumulated at a lower abundance relative to that of pUL117.5. During HCMV infection, both proteins localized predominantly to the nucleus, and the major fraction of pUL117 localized in viral nuclear replication compartments. We constructed mutant HCMV viruses in which the entire UL117 coding sequence was deleted or the expression of pUL117 was specifically abrogated. The growth of mutant viruses was significantly attenuated, indicating that pUL117 was required for efficient virus infection in fibroblasts. Cells infected with the pUL117-deficient mutant virus accumulated representative viral immediate-early proteins and early proteins normally. In the absence of pUL117, the accumulation of replicating viral DNA was reduced by no more than twofold at early times and was indistinguishable from that of the wild type at 72 h postinfection. Strikingly, there was a 12- to 24-h delay in the development of nuclear replication compartments and a marked delay in the expression of late viral proteins. We conclude that pUL117 acts to promote the development of nuclear replication compartments to facilitate viral growth.