132,990 research outputs found
Stability of the Bet v 1 cross-reactive allergens Api g 1 and Dau c 1 : a biophysical approach
No full textThe allergen Bet v 1 is known as the primary sensitizer for birch pollen-related food allergy and is responsible for IgE cross-reactivity to pathogenesis-related 10 (PR-10) proteins from, in particular, fruits from the Rosaceae and vegetables from the Apiaceae families. The allergenic potential of PR-10 proteins is mainly characterized for specific recombinantly produced isoforms, which are used for research and diagnostic purposes. However, in natural food sources these allergens are often present as isoform mixtures. The first aim of this research was to purify and characterize PR-10 allergens as natural isoform mixtures to determine whether differences could be observed between natural and recombinant allergens and between plant families. The second aim was to find a relationship between the physico-chemical stability of PR-10 proteins and structural characteristics to explain differences in IgE binding potential and cross-reactivity. The PR-10 allergens Bet v 1 from birch, Api g 1 from celery, and Dau c 1 from carrot were purified under mild conditions following a standardized protocol. Different allergen isoforms were determined and circular dichorism (CD) analyses of the allergen mixtures showed a similar secondary structure composition as observed for other PR-10 proteins. The allergen mixtures and recombinant allergens were characterized by stability studies to pH, temperature and denaturant where CD was used to detect structural changes. Minor differences were observed in stability between natural isoform mixtures and between the recombinant isoforms, although recombinant Dau c 1 was likely destabilized by its attached His-tag. A general trend was observed for allergen stability, structural differences and their relationship to the IgE binding capacity in aqueous solutions. The allergenic potential decreases in the following order: Bet v 1, the primary allergen of birch pollen-related allergies, Mal d 1, Api g 1 and Dau c 1, in accordance with their amino acid sequence identity. Bet v 1 cross-reactive IgE antibodies preferably bind to the charged and polar residues of Mal d 1 for which the positive charge can be increased by the physiological pH of fruit. Api g 1 appears to be more stable than Dau c 1 as the result of a tighter hydrophobic packing. However, the thermodynamic stability of Api g 1 is similar to that of Bet v 1, but the higher proportion of hydrophobic residues and the reduced proportion of charged residues are responsible for the lower IgE binding capacity. Furthermore, the IgE binding capacity is not severely affected, as long as the protein is able to refold. The implications of these findings are discussed in the context of the development of allergic symptoms upon exposure to these PR-10 proteins. <br/
The DAU Allele and Anti-D Alloimmunization Present With High Frequency in Brazilian Sickle Cell Disease Patients
No full textBrazilian National Council of Research (CNPq) (3065427/2007-5 and 484457/2007-1) (M.S.G.); the Foundation of Research and Extension of Bahia (FAPESB) (1431040053063; 9073/2007
and 6234/2010) (M.S.G.); and MCD/CNPq/MS-SCTIEDECIT (409800/2006-6) (M.S.G.).Background: Antigens DIIIa, DAR and DAU are common in people
of African descent and are involved in anti-D alloimmunization.
Sickle cell disease (SCD) patients frequently need blood therapy and
are vulnerable to alloimmunization.
Methods: The study included SCD patients from the Brazilian state
of Bahia, which has the highest incidence of the disease in Brazil; 241
SCD patients and 220 healthy individuals were studied. Alleles were
characterized by PCR-RFLP and PCR-SSP techniques.
Results: The DAU allele was found in 22.3% (43/193) of the SCD
patients. Two (1%) patients had the DIIIa/D wild-type genotype, one
(0.5%) had the DIIIa/D- genotype, 11 (5.7%) had the DAR/D wildtype
genotype and three (1.6%) had the DAR/D- genotype. Two patients
were positive for the 667T>G mutation and the 1136C>T mutation,
one (0.5%) had the genotype DIIIa/DAU, and one (0.5%) had
the genotype DAR/DAU.
Conclusion: There was statistical significance when the allele frequencies
were evaluated among SCD, sickle cell anemia (HbSS)
patients and healthy individuals. The frequencies of the DIIIa, DAR
and DAU alleles among SCD patients differ from those of healthy
individuals from the same population, and a high frequency of the
DAU variant was associated with anti-D alloimmunization in these
patients
The DAU Allele and Anti-D Alloimmunization Present With High Frequency in Brazilian Sickle Cell Disease Patients
No full textBrazilian National Council of Research (CNPq) (3065427/2007-5 and 484457/2007-1) (M.S.G.); the Foundation of Research and Extension of Bahia (FAPESB) (1431040053063; 9073/2007
and 6234/2010) (M.S.G.); and MCD/CNPq/MS-SCTIEDECIT (409800/2006-6) (M.S.G.).Universidade Federal do Amazonas. Faculdade de Farmacia. Manaus, AM, BrasilUniversidade do Estado da Bahia. Departamento de Ciencias da Vida. Salvador, BA, BrasilUniversidade Federal do Amazonas. Faculdade de Farmacia. Manaus, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia, Salvador, BA, BrasilBackground: Antigens DIIIa, DAR and DAU are common in people
of African descent and are involved in anti-D alloimmunization.
Sickle cell disease (SCD) patients frequently need blood therapy and
are vulnerable to alloimmunization.
Methods: The study included SCD patients from the Brazilian state
of Bahia, which has the highest incidence of the disease in Brazil; 241
SCD patients and 220 healthy individuals were studied. Alleles were
characterized by PCR-RFLP and PCR-SSP techniques.
Results: The DAU allele was found in 22.3% (43/193) of the SCD
patients. Two (1%) patients had the DIIIa/D wild-type genotype, one
(0.5%) had the DIIIa/D- genotype, 11 (5.7%) had the DAR/D wildtype
genotype and three (1.6%) had the DAR/D- genotype. Two patients
were positive for the 667T>G mutation and the 1136C>T mutation,
one (0.5%) had the genotype DIIIa/DAU, and one (0.5%) had
the genotype DAR/DAU.
Conclusion: There was statistical significance when the allele frequencies
were evaluated among SCD, sickle cell anemia (HbSS)
patients and healthy individuals. The frequencies of the DIIIa, DAR
and DAU alleles among SCD patients differ from those of healthy
individuals from the same population, and a high frequency of the
DAU variant was associated with anti-D alloimmunization in these
patients
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
H/D Isotope Effects Reveal Factors Controlling Catalytic Activity in Co-Based Oxides for Water Oxidation
No full textUnderstanding the mechanism for electrochemical water oxidation is important for the development of more efficient catalysts for artificial photosynthesis. A basic step is the proton-coupled electron transfer, which enables accumulation of oxidizing equivalents without buildup of a charge. We find that substituting deuterium for hydrogen resulted in an 87% decrease in the catalytic activity for water oxidation on Co-based amorphous-oxide catalysts at neutral pH, while 160-to-180 substitution lead to a 10% decrease. In situ visible and quasi-in situ X-ray absorption spectroscopy reveal that the hydrogen-to-deuterium isotopic substitution induces an equilibrium isotope effect that shifts the oxidation potentials positively by approximately 60 mV for the proton coupled Co-II/III and Co-II/III electron transfer processes. Time resolved spectroelectrochemical measurements indicate the absence of a kinetic isotope effect, implying that the precatalytic proton-coupled electron transfer happens through a stepwise mechanism in which electron transfer is rate-determining. An observed correlation between Co oxidation states and catalytic current for both isotopic conditions indicates that the applied potential has no direct effect on the catalytic rate, which instead depends exponentially on the average Co oxidation state. These combined results provide evidence that neither proton nor electron transfer is involved in the catalytic rate-determining step. We propose a mechanism with an active species composed by two adjacent Cow atoms and a rate-determining step that involves oxygen oxygen bond formation and compare it with models proposed in the literature
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