Transthyretin: a review from a structural perspective

Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism of amyloid formation and detecting the variant gene in individuals at risk. Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001     

Dynamics of collapsing and exploding Bose-Einstein condensates.

When atoms in a gas are cooled to extremely low temperatures, they will-under the appropriate conditions-condense into a single quantum-mechanical state known as a Bose-Einstein condensate. In such systems, quantum-mechanical behaviour is evident on a macroscopic scale. Here we explore the dynamics of how a Bose-Einstein condensate collapses and subsequently explodes when the balance of forces governing its size and shape is suddenly altered. A condensate's equilibrium size and shape is strongly affected by the interatomic interactions. Our ability to induce a collapse by switching the interactions from repulsive to attractive by tuning an externally applied magnetic field yields detailed information on the violent collapse process. We observe anisotropic atom bursts that explode from the condensate, atoms leaving the condensate in undetected forms, spikes appearing in the condensate wavefunction and oscillating remnant condensates that survive the collapse. All these processes have curious dependences on time, on the strength of the interaction and on the number of condensate atoms. Although the system would seem to be simple and well characterized, our measurements reveal many phenomena that challenge theoretical models.     

Gene polymorphism in Netherton and common atopic disease.

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.     

Protein constituents of the eggshell: eggshell-specific matrix proteins

In this article, we review the results of recent proteomic and genomic analyses of eggshell matrix proteins and draw attention to the impact of these data on current understanding of eggshell formation and function. Eggshell-specific matrix proteins from avian (ovocleidins and ovocalyxins) and non-avian (paleovaterin) shells are discussed. Two possible roles for eggshell-specific matrix proteins have been proposed; both reflect the protective function of the eggshell in avian reproduction: regulation of eggshell mineralization and antimicrobial defense. An emerging concept is the dual role (mineralization/antimicrobial protection) that certain eggshell matrix proteins can play.     

Effects of maternal aging on localizations and expression levels of DNA methyltransferases and chromosome architecture in in-vivo matured mouse oocytes

This paper investigated the age-related changes in the expression patterns of maintenance methyltransferase (DNMT1) and de novo methyltransferases (DNMT3a, 3b, 3L) and the chromosome architecture in in-vivo matured mouse oocytes using two-photon laser-scanning microscope. Our results showed that (1) DNMT1 and DNMT3a, 3b, 3L in the oocytes of pubertal mice were located in the cortical region of oocyte cytoplasm. In aging groups, DNMT1 was also located in the cortical region. However, DNMT3a, 3b, 3L had a relatively wider distribution in the oocyte cytoplasm and appeared near the chromosomes. These differences between pubertal and aging groups suggested that aging might affect DNA methylation; (2) the expression of DNMT1, and DNMT3a, 3b in aging groups increased significantly compared to pubertal groups, while, the expression of DNMT3L decreased. These results might be explained by the compensation mechanism among DNMTs, which might be impervious to aging; (3) aging caused increased errors in the distribution and three-dimensional morphology of chromosomes, including the increased total volume and surface area, the high ratio of height to diameter of a circular cylinder enclosing the chromosomes (H/D). Our work provided morphological information for the studies of age-related decline in oocyte qualities.     

Equilibrating metal-oxide cluster ensembles for oxidation reactions using oxygen in water.

Although many enzymes can readily and selectively use oxygen in water-the most familiar and attractive of all oxidants and solvents, respectively-the design of synthetic catalysts for selective water-based oxidation processes utilizing molecular oxygen remains a daunting task. Particularly problematic is the fact that oxidation of substrates by O2 involves radical chemistry, which is intrinsically non-selective and difficult to control. In addition, metallo-organic catalysts are inherently susceptible to degradation by oxygen-based radicals, while their transition-metal-ion active sites often react with water to give insoluble, and thus inactive, oxides or hydroxides. Furthermore, pH control is often required to avoid acid or base degradation of organic substrates or products. Unlike metallo-organic catalysts, polyoxometalate anions are oxidatively stable and are reversible oxidants for use with O2 (refs 8,9,10). Here we show how thermodynamically controlled self-assembly of an equilibrated ensemble of polyoxometalates, with the heteropolytungstate anion [AIVVW11O40]6- as its main component, imparts both stability in water and internal pH-management. Designed to operate at near-neutral pH, this system facilitates a two-step O2-based process for the selective delignification of wood (lignocellulose) fibres. By directly monitoring the central Al atom, we show that equilibration reactions typical of polyoxometalate anions keep the pH of the system near 7 during both process steps.     

Individual recognition in mice mediated by major urinary proteins.

The ability to recognize individuals is essential to many aspects of social behaviour, such as the maintenance of stable social groups, parent-offspring or mate recognition, inbreeding avoidance and the modulation of competitive relationships. Odours are a primary mediator of individuality signals among many mammals. One source of odour complexity in rodents, and possibly in humans, resides in the highly polymorphic major histocompatibility complex (MHC). The olfactory acuity of mice and rats allows them to distinguish between the urinary odours of congenic strains differing only in single genes within the MHC, although the chemical mediators or odorants are unknown. However, rodent urine also contains a class of proteins, termed major urinary proteins (MUPs), that bind and release small volatile pheromones. We have shown that the combinatorial diversity of expression of MUPs among wild mice might be as great as for MHC, and at protein concentrations a million times higher. Here we show in wild house mice (Mus domesticus) that urinary MUPs play an important role in the individual recognition mechanism.     

浅议图书馆复印保障部门的辅助功能及其管理

介绍了图书馆以文献复印为主的有偿服务部门的辅助功能,探讨了部室以人为本的管理理念。     

Beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation

The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression, and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation.