Synthesis and structural characterization of piperazino-modified DNA that favours hybridization towards DNA over RNA

We report the synthesis of two C4′-modified DNA analogues and characterize their structural impact on dsDNA duplexes. The 4′-C-piperazinomethyl modification stabilizes dsDNA by up to 5°C per incorporation. Extension of the modification with a butanoyl-linked pyrene increases the dsDNA stabilization to a maximum of 9°C per incorporation. Using fluorescence, ultraviolet and nuclear magnetic resonance (NMR) spectroscopy, we show that the stabilization is achieved by pyrene intercalation in the dsDNA duplex. The pyrene moiety is not restricted to one intercalation site but rather switches between multiple sites in intermediate exchange on the NMR timescale, resulting in broad lines in NMR spectra. We identified two intercalation sites with NOE data showing that the pyrene prefers to intercalate one base pair away from the modified nucleotide with its linker curled up in the minor groove. Both modifications are tolerated in DNA:RNA hybrids but leave their melting temperatures virtually unaffected. Fluorescence data indicate that the pyrene moiety is residing outside the helix. The available data suggest that the DNA discrimination is due to (i) the positive charge of the piperazino ring having a greater impact in the narrow and deep minor groove of a B-type dsDNA duplex than in the wide and shallow minor groove of an A-type DNA:RNA hybrid and (ii) the B-type dsDNA duplex allowing the pyrene to intercalate and bury its apolar surface

Is comorbidity in adolescence a predictor for adult low back pain? A prospective study of a young population

BACKGROUND: It has previously been shown that low back pain (LBP) often presents already in the teenage years and that previous LBP predicts future LBP. It is also well documented that there is a large degree of comorbidity associated with LBP, both in adolescents and adults. The objective of this study is to gain a deeper insight into the etiology of low back pain and to possibly develop a tool for early identification of high-risk groups. This is done by investigating whether different types of morbidity in adolescence are associated with LBP in adulthood. METHODS: Almost 10,000 Danish twins born between 1972 and 1982 were surveyed by means of postal questionnaires in 1994 and again in 2002. The questionnaires dealt with various aspects of general health, including the prevalence of LBP, classified according to number of days affected during the previous year (0, 1–7, 8–30, >30). The predictor variables used in this study were LBP, headache, asthma and atopic disease at baseline; the outcome variable was persistent LBP (>30 days during the past year) at follow-up. Associations between morbidity in 1994 and LBP in 2002 were investigated. RESULTS: LBP, headache and asthma in adolescence were positively associated with future LBP. There was no association between atopic disease and future LBP. Individuals with persistent LBP at baseline had an odds ratio of 3.5 (2.8–4.5) for future LBP, while the odds ratio for those with persistent LBP, persistent headache and asthma was 4.5 (2.5–8.1). There was a large degree of clustering of these disorders, but atopic disease was not part of this pattern. CONCLUSION: Young people from 12 to 22 years of age with persistent LBP during the previous year have an odds ratio of 3.5 persistent LBP eight years later. Both headache and asthma are also positively associated with future LBP and there is a large clustering of LBP, headache and asthma in adolescence

“Es fundamental que la información que se transmita sea confiable”

El flamante Doctor Honoris Causa de la UNLP, Emilio Luque Fadón, de la Universidad Autónoma de Barcelona, fue uno de los conferencistas de CACIC 2017. Durante su estadía por la ciudad de La Plata, el español habló acerca de las nuevas tecnologías, su tolerancia a los fallos y el consumo energético.Facultad de Informátic