17 research outputs found
THE OPERATION BY THE EDUCATION PROVIDERS AND LEARNING SPACES AT INDEPENDENT SCHOOLS IN SWEDEN
ANALYSIS ON THE SPACE LAYOUT AND FIELD OF CHILDREN'S ACTIVITIES FROM THE VIEW POINT OF GRADE
Differential activities of two distinct endothelin family peptides on ileum and coronary artery
Investigation of Maternal Diet and <i>FADS1</i> Polymorphism Associated with Long-Chain Polyunsaturated Fatty Acid Compositions in Human Milk
Increasing the amount of long-chain polyunsaturated fatty acids (LCPUFA) in human milk is an important strategy for infant growth and development. We investigated the associations of LCPUFA compositions in human milk with maternal diet (especially fish and shellfish intake), with fatty acid Δ5 desaturase gene (FADS1) polymorphisms, and with gene-diet interactions. The present study was performed as part of an adjunct study of the Japan Environment and Children’s Study. The participants were 304 lactating females, who provided human milk 6–7 months after delivery. Fatty acids in human milk were analyzed by gas chromatography, and dietary surveys were conducted using a brief self-administered diet history questionnaire. We also analyzed a single nucleotide polymorphism of FADS1 (rs174547, T/C). There was a significant difference in arachidonic acid (ARA) composition in human milk among the genotype groups, and the values were decreasing in the order of TT > TC > CC. The concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also different between TT and CC genotype, indicating a tendency for decreasing values in the same order. The composition of ARA showed significant gene–dietary interactions in multiple regression analysis, and the positive correlation between fish and shellfish intake and ARA composition in human milk was significant only in the CC genotype. Moreover, the factor most strongly associated with EPA and DHA composition in human milk was fish and shellfish intake. Therefore, it was suggested that increasing fish and shellfish intake in mothers may increase EPA and DHA composition in human milk, while increasing fish and shellfish intake in CC genotype mothers may lead to increased ARA composition in human milk
Extensive Survey of Antibody Invariant Positions for Efficient Chemical Conjugation Using Expanded Genetic Codes
The
site-specific chemical conjugation of proteins, following synthesis
with an expanded genetic code, promises to advance antibody-based
technologies, including antibody drug conjugation and the creation
of bispecific Fab dimers. The incorporation of non-natural amino acids
into antibodies not only guarantees site specificity but also allows
the use of bio-orthogonal chemistry. However, the efficiency of amino
acid incorporation fluctuates significantly among different sites,
thereby hampering the identification of useful conjugation sites.
In this study, we applied the codon reassignment technology to achieve
the robust and efficient synthesis of chemically functionalized antibodies
containing <i>N</i><sup>ε</sup>-(<i>o</i>-azidobenzyloxycarbonyl)-l-lysine (<i>o</i>-Az-Z-Lys)
at defined positions. This lysine derivative has a bio-orthogonally
reactive group at the end of a long side chain, enabling identification
of multiple new positions in Fab-constant domains, allowing chemical
conjugation with high efficiency. An X-ray crystallographic study
of a Fab variant with <i>o</i>-Az-Z-Lys revealed high-level
exposure of the azido group to solvent, with six of the identified
positions subsequently used to engineer “Variabodies”,
a novel antibody format allowing various connections between two Fab
molecules. Our findings indicated that some of the created Variabodies
exhibited agonistic activity in cultured cells as opposed to the antagonistic
nature of antibodies. These results showed that our approach greatly
enhanced the availability of antibodies for chemical conjugation and
might aid in the development of new therapeutic antibodies