University of Tsukuba

About: University of Tsukuba is a education organization based out in Tsukuba, Ibaraki, Japan. It is known for research contribution in the topics: Population & Gene. The organization has 36352 authors who have published 79483 publications receiving 1934752 citations. The organization is also known as: Tsukuba daigaku & Tsukuba University.

Volume transition in a gel driven by hydrogen bonding

Abstract: INTERACTIONS between macromolecules fall into four categories: ionic, hydrophobic, van der Waals and hydrogen bonding. Phase transitions in polymer gels provide a means of studying these interactions. Many gels will undergo reversible, discontinuous volume changes in response to changes in, for example, temperature, gel composition or light irradiation1–5. These transitions result from the competition between repulsive intermolecular forces, usually electrostatic in nature, that act to expand the polymer network, and an attractive force that acts to shrink it. Volume transitions in gels have been observed that are driven by all of the above-mentioned forces except hydrogen bonding (ref 6–10; T.T. et al, unpublished data; H. Inomata et al., personal communication). Here we report on a phase transition in an interpenetrating polymer network of poly(acrylamide) and poly(acrylic acid) that completes this picture—it is controlled by cooperative 'zipping' interactions between the molecules which result from hydrogen bonding. Cooperativity is an essential feature of the interactions, in that independent hydrogen bonds would not provide a sufficient driving force for the transition. A further novel characteristic of this phase transition is that the swelling (in water) is induced by an increase rather than a decrease in temperature.

Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity.

Abstract: Keap1 and Cul3 constitute a unique ubiquitin E3 ligase that degrades Nrf2, a key activator of cytoprotective genes. Upon exposure to oxidants/electrophiles, the enzymatic activity of this ligase complex is inhibited and the complex fails to degrade Nrf2, resulting in the transcriptional activation of Nrf2 target genes. Keap1 possesses several reactive cysteine residues that covalently bond with electrophiles in vitro. To clarify the functional significance of each Keap1 cysteine residue under physiological conditions, we established a transgenic complementation rescue model. The transgenic expression of mutant Keap1(C273A) and/or Keap1(C288A) protein in Keap1 null mice failed to reverse constitutive Nrf2 activation, indicating that cysteine residues at positions 273 and 288 are essential for Keap1 to repress Nrf2 activity in vivo. In contrast, Keap1(C151S) retained repressor activity and mice expressing this molecule were viable. Mouse embryonic fibroblasts from Keap1(C151S) transgenic mice displayed decreased expression of Nrf2 target genes both before and after an electrophilic challenge, suggesting that Cys151 is important in facilitating Nrf2 activation. These results demonstrate critical roles of the cysteine residues in vivo in maintaining Keap1 function, such that Nrf2 is repressed under quiescent conditions and active in response to oxidants/electrophiles.

A Functional Polymorphism in the Promoter Region of the Dopamine D2 Receptor Gene Is Associated with Schizophrenia

Abstract: An excess dopaminergic activity may be implicated in the etiology of schizophrenia. Our objective was to identify nucleotide variants in the 5' region of the dopamine D2 receptor gene (DRD2) and to clarify their effects on schizophrenia. We identified two polymorphisms, the A-241G and -141C Ins/Del, by examination of 259 bp in the 5'-flanking region and 249 bp of exon 1 of DRD2. Reporter constructs containing the -141C Del allele cloned into a luciferase reporter plasmid drove 21% (Y-79 cells) and 43% (293 cells) expression compared with the -141C Ins allele. In a case-control study, the -141C Del allele frequency was significantly lower in 260 schizophrenic patients than in 312 controls (OR = 0.60, 95%CI 0.44-0.81, P < 0.001). No significant association was found between the A-241G polymorphism and in vitro luciferase activity, or in allele frequency between the patients versus controls. These findings show that the -141C Ins/Del may be a functional polymorphism in the 5'-promoter region of DRD2 and may affect the susceptibility to schizophrenia.