The Dimeric Form of 1,3-Diaminoisoquinoline Derivative Rescued the Mis-splicing of Atp2a1 and Clcn1 Genes in Myotonic Dystrophy Type 1 Mouse Model

Expanded CUG repeat RNA in the dystrophia myotonia protein kinase (DMPK) gene causes myotonic dystrophy type 1 (DM1) and sequesters RNA processing proteins, such as the splicing factor muscleblind-like 1 protein (MBNL1). Sequestration of splicing factors results in the mis-splicing of some pre-mRNAs. Small molecules that rescue the mis-splicing in the DM1 cells have drawn attention as potential drugs to treat DM1. Herein we report a new molecule JM642 consisted of two 1,3-diaminoisoquinoline chromophores having an auxiliary aromatic unit at the C5 position. JM642 alternates the splicing pattern of the pre-mRNA of the Ldb3 gene in the DM1 cell model and Clcn1 and Atp2a1 genes in the DM1 mouse model. In vitro binding analysis by surface plasmon resonance (SPR) assay to the r(CUG) repeat and disruption of ribonuclear foci in the DM1 cell model suggested the binding of JM642 to the expanded r(CUG) repeat in vivo, eventually rescue the mis-splicing.     

Photochromic DNA having fluorescent protein-inspired nucleosides

Molecular switches controlled by light stimuli can be applicable to the variety of the biological application. In this study, skeletal structures of a chromophore of fluorescent protein were applied as aglycones of newly designed photochromic nucleosides, “Fluorescent protein-inspired nuceloside: FIN”. Phosphoramidite units of the photochromic nucleosides having imidazolinone derivatives with benzylidene or 3-pyridilidene groups were successfully synthesized for FIN-containing ODNs. Thermodynamic studies of the FIN-containing ODNs revealed that photo-irradiation with specific wavelength induced stability change of the duplexes.     

Structure of native and regenerated cellulose as revealed by proton NMR analysis

Differences in fiber structure between cotton and cuprammonium rayon are studied by a refined broad-line proton NMR analysis of samples swollen with deuterated dimethyl sulfoxide, which has no effect on the spectra but enhances differences in molecular mobility between crystalline and noncrystalline regions. The spectra obtained are decomposed into four components: broad, medium, narrow, and extremely narrow. These components are identified as contributions, respectively, from crystalline and rigid noncrystalline (frozen glassy) material, a noncrystalline glassy component exhibiting local segmental motion, a noncrystalline rubbery component exhibiting liquidlike molecular motion, and protons included in DMSO-d₆ as an impurity. The mass fraction of the narrow component in cotton was about 0.01, whereas it was as high as 0.18 in cuprammonium rayon. It is concluded that even in the swollen state, native cellulose is devoid of a liquidlike mobile component, but regenerated cellulose contains a considerable amount of a noncrystalline component involving liquidlike segmental motion of molecules.     

Dichloromethylenation of esters and lactones by triphenylphosphine-carbon tetrachloride reagent

Reaction of triphenylphosphine-carbon tetrachloride reagent with esters and lactones produced 1-substituted 2,2-dichlorovinyl ethers. Hydrolysis of these ethers in acidic conditions afforded the dichloromethyl ketones.     

Control of 1D wave versus 2D honeycomb CoIIICdIICuI heterotrimetallic architectures by Delta L-Lambda L diastereoisomerism of L-cysteinatocobalt(III) building units

The reactions of the Delta L and Lambda L isomers of [Co( l-Hcys- N, S)(en) 2] (2+) ( l-H 2cys = l-cysteine) with CuCl in aqueous HCl gave Co (III)Cu (I) dinuclear complexes with the same S-bridged structures, Delta L- 1 and Lambda L- 1. When Delta L- 1 was treated with CdCl 2 in water, a 1D wavelike (Co (III) 2Cd (II)Cu (I)) n polymeric complex ( 2) was produced. On the other hand, similar treatment of Lambda L- 1 led to the formation of a 2D honeycomb-like (Co (III) 3Cd (II) 3Cu (I)) n polymeric complex ( 3), supported by the presence of counter-monoanions.     

Intrauterine devices and uterine peristalsis: evaluation with MRI

Intrauterine devices (IUDs) have been viewed as an effective form of contraception. However, the mechanism by which IUDs disturb fertility remains controversial. This study aimed to evaluate the effects of IUDs on uterine contractility using cine MR. Eleven healthy female volunteers of reproductive age bearing IUDs and 12 women not bearing IUDs were evaluated during the periovulatory phase. MR images were obtained with a 1.5-T magnet, acquiring 60 serial images every 3 s via half-Fourier acquisition single-shot turbo spin echo to be displayed on cine mode. Assessments were based on (a) the presence of peristaltic waves, (b) the frequency and direction of peristaltic waves and (c) the extent of peristaltic waves. Static images were evaluated for thickness of the junctional zone (JZ) and myometrium. A fundo-cervical (FC)-directed peristaltic wave was identified in 4 of 11 IUD-bearing subjects and in only 1 of 12 subjects from the control group. FC waves extended through more than half of the thickness of the myometrium. Peristaltic frequency in IUD users (5.0/3 min) was less than that of the control group (6.5/3 min). The JZ and myometrium were significantly thicker in IUD users. FC-directed waves were more often observed in IUD-bearing subjects, which might explain the inhibition of active sperm transport.