Formation of Direction-Controllable Pseudorotaxane and Catenane Using Chemically Cyclized Oligodeoxynucleotides and Their Noncovalent RNA Labeling.

The formation of interlocked structures, such as rotaxane and catenane, enables noncovalent conjugations. We previously confirmed that the chemically cyclized pseudorotaxane-forming oligodeoxynucleotides (prfODNs) with double-tailed parts formed a pseudorotaxane structure with the target DNA and RNA via the slipping process. Here, we report the one-step synthesis of cyclized prfODNs from alkyne-modified ODNs, after which we investigated the properties and mechanism of the slipping process and performed noncovalent RNA labeling with prfODNs. Additionally, the catenane structure was formed by the combination of pseudorotaxane formation with a 5'-end-phosphorylated RNA and enzymatic ligation. The newly synthesized prfODN represents a new tool for achieving the noncovalent conjugation of various functional moieties to RNAs.

Culture-dependent and universal constructs and promoting factors for the process of personal recovery in users of mental health services: qualitative findings from Japan.

BACKGROUND: The conceptualization of personal recovery began in Europe and North America and has spread worldwide. However, the concept of personal recovery in addition to recovery-promoting factors may be influenced by culture. We explored how users of mental health services in Japan perceive their own personal recovery and the factors that promote it. METHODS: We conducted semi-structured interviews and focus group interviews with individuals using mental health services. The interview data were analysed using thematic analysis with a grouped framework analysis approach. We used a coding framework based on the existing CHIME framework (connectedness, hope and optimism about the future, identity, meaning in life, and empowerment). RESULTS: Data were obtained from 30 users of mental health services (mean age: 40.4 years; 46.7% women; 50.0% with schizophrenia). "Compassion for others" was newly extracted in "Connectedness", and "Rebuilding/redefining identity not being as shaped by social norms" was newly extracted in "Identity" as personal recovery. "Positive experiences in childhood" (including positive parenting support from neighbours) was newly extracted as a recovery-promoting factor. CONCLUSIONS: Our unique findings on the rebuilding identity/defining identity free from conformity to social norms due to interactions with familiar people, including peers, may be culture dependent. This study raises overarching questions regarding how socio-cultural values influence the development of identity and personal values and how they are in turn reflected in personal recovery.

Rapid Alkene-Alkene Photo-Cross-Linking on the Base-Flipping-Out Field in Duplex DNA.

Specific chemical reactions by enzymes acting on a nucleobase are realized by flipping the target base out of the helix. Similarly, artificial oligodeoxynucleotides (ODNs) can also induce the base flipping and a specific chemical reaction. We now report an easily prepared and unique structure-providing photo-cross-linking reaction by taking advantage of the base-flipping-out field formed by alkene-type base-flipping-inducing artificial bases. Two 3-arylethenyl-5-methyl-2-pyridone nucleosides with the Ph or An group were synthesized and incorporated into the ODNs. We found that the two Ph derivatives provided the cross-linked product in a high yield only by a 10 s photoirradiation when their alkenes overlap each other in the duplex DNA. The highly efficient reaction enabled forming a cross-linked product even when using the duplex with a low Tm value.

Strong Binding and Off-On Signaling Functions of Deep-Red Fluorescent TO-PRO-3 for Influenza†A Virus RNA Promoter Region.

The RNA promoter region of the influenza A virus has recently attracted much attention as an RNA target for the development of anti-influenza drugs. However, there are very few reports on small RNA-binding ligands targeting this region. In this work, it is reported that TO-PRO-3, a thiazole orange analogue with a trimethine bridge, exhibits strong and selective binding to the internal loop structure of the influenza A virus RNA promoter. This binding accompanies the remarkable light-up response of TO-PRO-3 in the deep-red spectral region. By virtue of these binding and fluorescence signaling functions, TO-PRO-3 can act as a useful indicator for the assessment of the binding capabilities of various test compounds for this RNA region, with a view toward the development of anti-influenza drug candidates.

Trimethine cyanine dyes as deep-red fluorescent indicators with high selectivity to the internal loop of the bacterial A-site RNA.

We report that TO-PRO-3, a thiazole orange analogue with a trimethine bridge, functions as a deep-red fluorescent indicator for the internal loop structure of the bacterial (Escherichia coli) ribosomal decoding region of the aminoacyl-tRNA site (A-site), which enables the assessment of A-site binding capability of various test compounds including blue and even-green-emitting compounds.

Fluorescent Trimethylated Naphthyridine Derivative with an Aminoalkyl Side Chain as the Tightest Non-aminoglycoside Ligand for the Bacterial A-site RNA.

The bacterial ribosomal decoding region of the aminoacyl-tRNA site (A-site) is one of the most validated target RNAs for antibiotic agents. Although natural aminoglycosides are well-characterized A-site binding ligands, high off-target effects and the growing emergence of bacterial resistance against aminoglycosides limit their clinical use. To circumvent these concerns with the aminoglycoside family, non-aminoglycoside A-site binding ligands have great potential as novel antibiotics against bacterial infections. This work describes a new class of small heterocyclic ligands based on the 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND) structure for the bacterial (Escherichia coli) A-site. ATMND possessing an aminoethyl side chain is found to strongly and selectively bind to the internal loop of the A-site (Kd =0.44 µm; pH 7.0, I=0.06 m, 5 °C). Significantly, this ligand shows the tightest binding reported to date among non-aminoglycoside ligands. The binding study based on the thermodynamics and molecular modelling reveals key molecular interactions of ATMND-C2 -NH2 for high affinity to the A-site. This ligand is also demonstrated to be applicable to the fluorescence indicator displacement assay for assessing ligand/A-site interactions.