Alignment of iodine species in stretched polyacetylene films

The¹²⁹I Mössbauer spectroscopy has been applied to iodine-doped highly conducting polyacetylene. For the unstretched polyacetylene films, the iodine species of I^?, I ₃ ^? and I ₅ ^? are observed. The polyiodides have symmetrical charge population. In addition to these anions, a small amount of iodines is covalently bonding to the carbon atoms, breaking the double bonds of the main chain. For the stretched polyacetylene films, the measurements were done under the condition that the stretch direction was parallel or perpendicular to the direction of incident ψ-rays. The relative change of the intensities of the Mössbauer quadrupole-split lines reveals the alignment of the polyiodine anions in the stretched film.     

Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic site

Clustered DNA damage sites induced by ionizing radiation have been suggested to have serious consequences to organisms, such as cancer, due to their reduced probability to be repaired by the enzymatic repair machinery of the cell. Although experimental results have revealed that clustered DNA damage sites effectively retard the efficient function of repair enzymes, it remains unclear as to what particular factors influence this retardation. In this study, approaches based on molecular dynamics (MD) simulation have been applied to examine conformational changes and energetic properties of DNA molecules containing clustered damage sites consisting of two lesioned sites, namely 7,8-dihydro-8-oxoguanine (8-oxoG) and apurinic/apyrimidinic (AP) site, located within a few base pairs of each other. After 1 ns of MD simulation, one of the six DNA molecules containing a clustered damage site develops specific characteristic features: sharp bending at the lesioned site and weakening or complete loss of electrostatic interaction energy between 8-oxoG and bases located on the complementary strand. From these results it is suggested that these changes would make it difficult for the repair enzyme to bind to the lesions within the clustered damage site and thereby result in a reduction of its repair capacity.     

Use of a retroinverso p53 peptide as an inhibitor of MDM2

An N-terminal helical region of the tumor suppressor p53 binds in a hydrophobic cleft of the oncoprotein MDM2. A retroinverso isomer of the natural N-terminal helical peptide was found to interact with MDM2 using the same hydrophobic residues, Phe, Trp, and Leu. We propose that the retroinverso d-peptide adopts a right-handed helical conformation to achieve functional mimicry of the p53 peptide.     

Frequency Dependence of ESR in Pristine Trans-Polyacetylene: Line Width

We measured a frequency dependence of ESR line width in (CH)x and (CD)x at frequencies 5～9,500 MHz. From a detailed analysis we could independently deduce 1-D diffusion rate of electron spin (neutral soliton) D_‖ /c_‖ ², and the trapped spin concentration C between 200 and 340 K.     

A fluorescent single domain antibody against plumbagin expressed in silkworm larvae for fluorescence-linked immunosorbent assay (FLISA)

A fluorescent single-domain antibody (fluobody), a chimera of a green fluorescent protein (AcGFP) with a single chain variable fragment antibody (scFv), against plumbagin (5-hydorxy-2-methyl-1,4-naphthoquinone; PL) was successfully expressed in the hemolymph of silkworm larvae using a Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA system to develop a rapid, simple, and sensitive fluorescence-linked immunosorbent assay (FLISA). In this study, two kinds of fluobody, in which the PL-scFv was fused at the N-terminus (N-fluobody) or C-terminus of AcGFP (C-fluobody), were expressed in silkworm larvae for comparative purposes. Interestingly, both fluobodies expressed in the BmNPV bacmid DNA system retained both of their original functions as an AcGFP and a PL-scFv, although the functions of the N-fluobody were found to be inferior to those of C-fluobody when they were expressed in Escherichia coli. Moreover, an improvement in the limit of quantification for PL measurement was observed in FLISA (24 ng mL(-1)) compared with conventional ELISA (0.2 μg mL(-1)). Since both the C-fluobody and N-fluobody are useful probes for FLISA and the time-, cost-consuming refolding step required in the conventional bacterial expression system can be avoided when they are expressed in the BmNPV bacmid DNA system, the silkworm expression system is useful for expressing fluobodies when developing FLISA.     

Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine

As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer.     

Recognition of tandem sialic acid residues by CD38: a theoretical study

The electronic structures of gangliosides are described using semiempirical and ab inito molecular orbital theories as well as the density functional theory to clarify the causative factors of the differences in inhibitory effects and to elucidate the recognition mechanisms of the enzyme. Our results suggest that CD38 is likely to recognize the two phosphate groups in NAD and the two carboxyl groups in tandem sialic acid residues of gangliosides. The recognition mechanisms of the substrate are proposed based on the good correlation found between the orbital energy of the highest occupied molecular orbital of the gangliosides and the degree of the inhibitory effect.     

Rudin's Dowker space, strong base-normality and base-strong-zero-dimensionality

It is well known that every pair of disjoint closed subsets F₀,F₁ of a normal T₁-space X admits a star-finite open cover U of X such that, for every U∈U, either or holds. We define a T₁-space X to be strongly base-normal if there is a base B for X with |B|=w(X) satisfying that every pair of disjoint closed subsets F₀,F₁ of X admits a star-finite cover B^′ of X by members of B such that, for every B∈B^′, either or holds. We prove that there is a base-normal space which is not strongly base-normal. Moreover, we show that Rudin's Dowker space is strongly base-(collectionwise)normal. Strong zero-dimensionality on base-normal spaces are also studied.