bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-idiotypic antibodies: a new approach in prion research
Authors: Colja Venturini Anja , Bresjanac Maja , Vranac Tanja , Koren Simon , Narat Mojca , Popović Mara , Čurin Šerbec Vladka 
Published: April 2009

AbstractBackgroundIn certain cases, anti-idiotypic antibodies that recognize an antigen-combining site of an antibody can mimic the structure and/or function of certain nominal antigens. This feature makes them particularly useful if conventional experimental approaches fail to fulfil expectations, especially when the molecule of interest is infectious, toxic or difficult to isolate and purify. We suggest the application of an anti-idiotype concept to the field of prion biology, with the aim of evoking a humoral immune response against the pathological isoform of the prion protein (PrPSc). Different ways to induce anti-idiotypic responses were studied in mice and chickens using various forms of V5B2, a PrPSc-specific monoclonal antibody we have described previously.ResultsThe preparation of anti-idiotypic monoclonal antibodies was achieved with well-defined strategies of immunization, selection and subsequent characterization. Our results demonstrate that it is possible to induce a strong anti-idiotypic immune response against the V5B2 monoclonal antibody in both xenogeneic and syngeneic experimental systems. From the competition seen between polyclonal and monoclonal anti-idiotypic antibodies and the original immunogen, the P1 peptide, and even more importantly, the ultimate target antigen, PrPSc, we conclude that selected antibodies bind to the antigen-combining site of the V5B2 monoclonal antibody and might even resemble the PrPSc-specific epitope. The involvement of both antigen-combining sites in the interaction between V5B2 and the most promising monoclonal anti-idiotypic antibody was further supported by molecular docking.ConclusionThe results of the present study not only provide an example of the successful production of Ab2 monoclonal antibodies based on a well planned strategy for selection, but should also provide a new experimental approach that is applicable to the field of prion diseases.
Lab on a chip genotyping for Brucella spp. based on 15-loci multi locus VNTR analysis
Authors: De Santis Riccardo , Ciammaruconi Andrea , Faggioni Giovanni , D'Amelio Raffaele , Marianelli Cinzia , Lista Florigio 
Published: April 2009

Abstract

Background
Brucellosis is an important zoonosis caused by the genus Brucella. In addition Brucella represents potential biological warfare agents due to the high contagious rates for humans and animals. Therefore, the strain typing epidemiological tool may be crucial for tracing back source of infection in outbreaks and discriminating naturally occurring outbreaks versus bioterroristic event. A Multiple Locus Variable-number tandem repeats (VNTR) Analysis (MLVA) assay based on 15 polymorphic markers was previously described. The obtained MLVA band profiles may be resolved by techniques ranging from low cost manual agarose gels to the more expensive capillary electrophoresis sequencing. In this paper a rapid, accurate and reproducible system, based on the Lab on a chip technology was set up for Brucella spp. genotyping.

Results
Seventeen DNA samples of Brucella strains isolated in Sicily, previously genotyped, and twelve DNA samples, provided by MLVA Brucella VNTR ring trial, were analyzed by MLVA-15 on Agilent 2100. The DNA fragment sizes produced by Agilent, compared with those expected, showed discrepancies; therefore, in order to assign the correct alleles to the Agilent DNA fragment sizes, a conversion table was produced. In order to validate the system twelve unknown DNA samples were analyzed by this method obtaining a full concordance with the VNTR ring trial results.

Conclusion
In this paper we described a rapid and specific detection method for the characterization of Brucella isolates. The comparison of the MLVA typing data produced by Agilent system with the data obtained by standard sequencing or ethidium bromide slab gel electrophoresis showed a general concordance of the results. Therefore this platform represents a fair compromise among costs, speed and specificity compared to any conventional molecular typing technique.
Transcription profiles of hydrogenases related genes in the cyanobacterium Lyngbya majuscula CCAP 1446/4
Authors: Ferreira Daniela , Pinto Filipe , Moradas-Ferreira Pedro , Mendes Marta V , Tamagnini Paula 
Published: April 2009

Abstract

Background

Lyngbya majuscula CCAP 1446/4 is a N2-fixing filamentous nonheterocystous strain that contains two NiFe-hydrogenases: an uptake (encoded by hupSL) and a bidirectional enzyme (encoded by hoxEFUYH). The biosynthesis/maturation of NiFe-hydrogenases is a complex process requiring several accessory proteins for e.g. for the incorporation of metals and ligands in the active center (large subunit), and the insertion of the FeS clusters (small subunit). The last step in the maturation of the large subunit is the cleavage of a C-terminal peptide from its precursor by a specific endopeptidase. Subsequently, the mature large and small subunits can assemble forming a functional enzyme.

Results
In this work we demonstrated that, in L. majuscula, the structural genes encoding the bidirectional hydrogenase are cotranscribed, and that hoxW (the gene encoding its putative specific endopeptidase) is in the same chromosomal region but transcribed from a different promoter. The gene encoding the putative specific uptake hydrogenase endopeptidase, hupW, can be cotranscribed with the structural genes but it has its own promoter. hoxH, hupL, hoxW and hupW transcription was followed in L. majuscula cells grown under N2-fixing and non-N2-fixing conditions over a 12 h light/12 h dark cycle. The transcription of hoxH, hoxW and hupW did not vary remarkably in the conditions tested, while the hupL transcript levels are significantly higher under N2-fixing conditions with a peak occurring in the transition between the light and the dark phase. Furthermore, the putative endopeptidases transcript levels, in particular hoxW, are lower than those of the respective hydrogenase structural genes.

Conclusion
The data presented here indicate that in L. majuscula the genes encoding the putative hydrogenases specific endopeptidases, hoxW and hupW, are transcribed from their own promoters. Their transcript levels do not vary notably in the conditions tested, suggesting that HoxW and HupW are probably constantly present and available in the cells. These results, together with the fact that the putative endopeptidases transcript levels, in particular for hoxW, are lower than those of the structural genes, imply that the activity of the hydrogenases is mainly correlated to the transcription levels of the structural genes. The analysis of the promoter regions indicates that hupL and hupW might be under the control of different transcription factor(s), while both hoxH and xisH (hoxW) promoters could be under the control of LexA.
Co-regulated expression of HAND2 and DEIN by a bidirectional promoter with asymmetrical activity in neuroblastoma
Authors: Voth Harald , Oberthuer André , Simon Thorsten , Kahlert Yvonne , Berthold Frank , Fischer Matthias 
Published: April 2009

Abstract

Background

HAND2, a key regulator for the development of the sympathetic nervous system, is located on chromosome 4q33 in a head-to-head orientation with DEIN, a recently identified novel gene with stage specific expression in primary neuroblastoma (NB). Both genes are expressed in primary NB as well as most NB cell lines and are separated by a genomic sequence of 228 bp. The similar expression profile of both genes suggests a common transcriptional regulation mediated by a bidirectional promoter.

Results
Northern Blot analysis of DEIN and HAND2 in 20 primary NBs indicated concurrent expression levels of the two genes, which was confirmed by microarray analysis of 236 primary NBs (Pearson's correlation coefficient r = 0.65). While DEIN expression in the latter cohort was associated with stage 4S (p = 0.02), HAND2 expression was not associated with tumor stage. In contrast, both HAND2 and DEIN transcript levels were highly associated with age at diagnosis <12 months (p = 0.001). The intergenic region shows substantial homology in different species (89%, 72% and 53% identity between human and mouse, chicken and zebrafish, respectively) and contains many highly conserved putative transcription factor binding sites. Using luciferase reporter gene constructs, asymmetrical bidirectional promoter activity was found in four NB cell lines: In DEIN orientation, an average 3.4 fold increase in activity was observed as compared to the promoterless vector, whereas an average 15.4 fold activation was detected in HAND2 orientation. The presence of two highly conserved putative regulatory elements, one of which was shown to enhance HAND2 expression in branchial arches previously, displayed weak repressor activity for both genes.

Conclusion

HAND2 and DEIN represent a gene pair that is tightly linked by a bidirectional promoter in an evolutionary highly conserved manner. Expression of both genes in NB is co-regulated by asymmetrical activity of this promoter and modulated by the activity of two cis-regulatory elements acting as weak repressors. The concurrent quantitative and tissue specific expression of HAND2 and DEIN suggests a functional link between both genes.
No relationship between 2',3'-cyclic nucleotide 3'-phosphodiesterase and schizophrenia in the Chinese Han population: an expression study and meta-analysis
Authors: Che Ronglin , Tang Wei , Zhang Jing , Wei Zhiyun , Zhang Zhao , Huang Ke , Zhao Xinzhi , Gao Jianjun , Zhou Guoquan , Huang Peirong , He Lin , Shi Yongyong 
Published: April 2009

Abstract

Background
2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP), one of the promising candidate genes for schizophrenia, plays a key part in the oligodendrocyte function and in myelination. The present study aims to investigate the relationship between CNP and schizophrenia in the Chinese population and the effect of different factors on the expression level of CNP in schizophrenia.

Methods
Five CNP single nucleotide polymorphisms (SNPs) were investigated in a Chinese Han schizophrenia case-control sample set (n = 180) using direct sequencing. The results were included in the following meta-analysis. Quantitative real-time polymerase chain reaction (PCR) was conducted to examine CNP expression levels in peripheral blood lymphocytes.

Results
Factors including gender, genotype, sub-diagnosis and antipsychotics-treatment were found not to contribute to the expression regulation of the CNP gene in schizophrenia. Our meta-analysis produced similar negative results.

Conclusion
The results suggest that the CNP gene may not be involved in the etiology and pathology of schizophrenia in the Chinese population.
Prediction of breast cancer by profiling of urinary RNA metabolites using Support Vector Machine-based feature selection
Authors: Henneges Carsten , Bullinger Dino , Fux Richard , Friese Natascha , Seeger Harald , Neubauer Hans , Laufer Stefan , Gleiter Christoph H , Schwab Matthias , Zell Andreas , Kammerer Bernd 
Published: April 2009

Abstract

Background
Breast cancer belongs to the most frequent and severe cancer types in human. Since excretion of modified nucleosides from increased RNA metabolism has been proposed as a potential target in pathogenesis of breast cancer, the aim of the present study was to elucidate the predictability of breast cancer by means of urinary excreted nucleosides.

Methods
We analyzed urine samples from 85 breast cancer women and respective healthy controls to assess the metabolic profiles of nucleosides by a comprehensive bioinformatic approach. All included nucleosides/ribosylated metabolites were isolated by cis-diol specific affinity chromatography and measured with liquid chromatography ion trap mass spectrometry (LC-ITMS). A valid set of urinary metabolites was selected by exclusion of all candidates with poor linearity and/or reproducibility in the analytical setting. The bioinformatic tool of Oscillating Search Algorithm for Feature Selection (OSAF) was applied to iteratively improve features for training of Support Vector Machines (SVM) to better predict breast cancer.

Results
After identification of 51 nucleosides/ribosylated metabolites in the urine of breast cancer women and/or controls by LC- ITMS coupling, a valid set of 35 candidates was selected for subsequent computational analyses. OSAF resulted in 44 pairwise ratios of metabolite features by iterative optimization. Based on this approach ultimately estimates for sensitivity and specificity of 83.5% and 90.6% were obtained for best prediction of breast cancer. The classification performance was dominated by metabolite pairs with SAH which highlights its importance for RNA methylation in cancer pathogenesis.

Conclusion
Extensive RNA-pathway analysis based on mass spectrometric analysis of metabolites and subsequent bioinformatic feature selection allowed for the identification of significant metabolic features related to breast cancer pathogenesis. The combination of mass spectrometric analysis and subsequent SVM-based feature selection represents a promising tool for the development of a non-invasive prediction system.
Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance
Authors: Schaetti Christian , Hutubessy Raymond , Ali Said M , Pach Al , Weiss Mitchell G , Chaignat Claire-Lise , Khatib Ahmed M 
Published: April 2009

Abstract

Background
Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral®).
Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest.
The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy.

Methods and design
Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance.

Discussion
The study presented here is designed to inform about people's perceptions regarding cholera and about socioeconomic and behavioural factors determining anticipated and actual oral cholera vaccine acceptance in Zanzibar. Its pre- and post-intervention design using a mixed-methods approach on different stakeholder levels in communities at high risk of cholera outbreaks will ensure the collection of locally valid data relevant for public health action and planning.
Development of reverse phase protein microarrays for the validation of clusterin, a mid-abundant blood biomarker
Authors: Aguilar-Mahecha Adriana , Cantin Christiane , O'Connor-McCourt Maureen , Nantel Andre , Basik Mark 
Published: April 2009

Abstract

Background
Many putative disease blood biomarkers discovered in genomic and proteomic studies await validation in large clinically annotated cohorts of patient samples. ELISA assays require large quantities of precious blood samples and are not high-throughput. The reverse phase protein microarray platform has been developed for the high-throughput quantification of protein levels in small amounts of clinical samples.

Results
In the present study we present the development of reverse-phase protein microarrays (RPPMs) for the measurement of clusterin, a mid-abundant blood biomarker. An experimental protocol was optimized for the printing of serum and plasma on RPPMs using epoxy coated microscope slides and a non-denaturing printing buffer. Using fluorescent-tagged secondary antibodies, we achieved the reproducible detection of clusterin in spotted serum and plasma and reached a limit of detection of 780 ng/mL. Validation studies using both spiked clusterin and clinical samples showed excellent correlations with ELISA measurements of clusterin.

Conclusion
Serum and plasma spotted in the reverse phase array format allow for reliable and reproducible high-throughput validation of a mid-abundant blood biomarker such as clusterin.
Function of anterior talofibular and calcaneofibular ligaments during in-vivo motion of the ankle joint complex
Authors: de Asla Richard J , Kozánek Michal , Wan Lu , Rubash Harry E , Li Guoan 
Published: April 2009

Abstract

Background
Despite the numerous in-vitro studies on the mechanical properties and simulated injury mechanisms of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), the in-vivo biomechanical behavior of these two ligaments has not yet been described.

Methods
Apparent length of the ATFL and CFL was measured in four ankles in healthy male subjects between 32 and 45 years of age (two left and two right) during a dorsiflexion-plantarflexion and supination-pronation arc of motion using a combined dual-orthogonal fluoroscopic and magnetic resonance imaging technique.

Results
The ATFL elongated from the neutral position at 16.3 +/- 3.0 mm to 20.8 +/- 2.7 mm at maximal plantarflexion and shortened significantly from the neutral position to 13.9 +/- 2.9 mm at maximal dorsiflexion (p = 0.01). The CFL shortened from the neutral position at 28.0 +/- 2.9 mm to 26.6 +/- 2.2 mm at maximal plantarflexion (p = 0.08) and elongated significantly from the neutral position to 29.9 +/- 3.0 mm at maximal dorsiflexion (p = 0.003). The ATFL elongated significantly from 14.8 +/- 2.5 mm at maximal pronation to 17.4 +/- 3.0 mm at maximal supination (p = 0.08). At the same time, the CFL shortened from 31.0 +/- 3.8 mm at maximal pronation to 26.9 +/- 3.6 mm at maximal supination (p = 0.02).

Conclusion
The results showed that the ATFL elongates more during plantarflexion and supination whereas the CFL increases in length with dorsiflexion and pronation. Concurrently, these data also demonstrated the reciprocal function between the two ligaments. While one shortens, the other one elongates. The different elongation of the ATFL and CFL during the same motion arc suggests that under excessive loading conditions the ATFL might be more vulnerable in plantarflexion and supination while the CFL might be more susceptible to injury in dorsiflexion and pronation. Furthermore, in the case of surgical reconstruction the grafts used to reconstruct the two ligaments may need to be tensioned at different positions of the ankle in order to reproduce their natural in vivo function.
Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma
Authors: Hauschild Axel , Agarwala Sanjiv S. , Trefzer Uwe , Hogg David , Robert Caroline , Hersey Peter , Eggermont Alexander , Grabbe Stephan , Gonzalez Rene , Gille Jens , Peschel Christian , Schadendorf Dirk , Garbe Claus , O'Day Steven , Daud Adil , White J. Michael , Xia Chenghua , Patel Kiran , Kirkwood John M. , Keilholz Ulrich 
Published: April 2009

Purpose This phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen. Patients and Methods A total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m2 plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively. Results The median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic events, grade 3 thrombocytopenia, diarrhea, and fatigue were more common in patients treated with sorafenib plus CP versus placebo plus CP. Conclusion In this study, the addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma. Both regimens had clinically acceptable toxicity profiles with no unexpected adverse events. A trial of similar design for the first-line treatment of patients with advanced melanoma (intergroup trial E2603) is currently ongoing.
The Effects of a Presurgical Stress Management Intervention for Men With Prostate Cancer Undergoing Radical Prostatectomy
Authors: Parker Patricia A. , Pettaway Curtis A. , Babaian Richard J. , Pisters Louis L. , Miles Brian , Fortier Adoneca , Wei Qi , Carr Danielle D. , Cohen Lorenzo 
Published: April 2009

Purpose This study assessed the short-term and long-term efficacy of a presurgical stress management intervention at reducing mood disturbance and improving quality of life (QOL) in men undergoing radical prostatectomy (RP) for prostate cancer. Patients and Methods One hundred fifty-nine men were randomly assigned to a two-session (plus two boosters) presurgical stress management intervention (SM), a two-session (plus two boosters) supportive attention group (SA), or a standard care group (SC). Assessments occurred 1 month before surgery; 1 week before surgery; the morning of surgery; 6 weeks after surgery, and 6 and 12 months after surgery. Results Results indicated significant group differences in mood disturbance before surgery (P = .02), such that men in the SM group had significantly less mood disturbance than men in the SC group (P = .006), with no significant differences between the SM and SA or SA and SC groups. In the year after surgery, there were significant group differences on Medical Outcomes Study 36-item short form survey (SF-36) physical component summary (PCS) scores (P = .004); men in the SM group had significantly higher PCS scores than men in the SC group (P = .0009), and there were no significant differences between the SM and SA or SA and SC groups. There were no group effects on prostate-specific QOL or SF-36 mental health scores. Conclusion These findings demonstrate the efficacy of a brief presurgical stress management intervention in improving some short-term and long-term outcomes. If these results are replicated, it may be a useful adjunct to standard care for men with prostate cancer undergoing surgery.