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The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Advances in microsensor technologies for air pollution monitoring encourage a growing use of portable sensors. This study aims at testing their performance in the development of exposure surfaces for nitrogen dioxide (NO2) and ozone (O3). In Montreal, Canada, a data-collection campaign was conducted across three seasons in 2014 for 76 sites spanning the range of land uses and built environments of the city; each site was visited from 6 to 12 times, for 20 min, using NO2 and O3 sensors manufactured by Aeroqual. Land-use regression models were developed, achieving R(2) values of 0.86 for NO2 and 0.92 for O3 when adjusted for regional meteorology to control for the fact that all of the locations were not monitored at the same time. A total of two exposure surfaces were then developed for NO2 and O3 as averages over spring, summer, and fall. Validation against the fixed-station data and previous campaigns suggests that Aeroqual sensors tend to overestimate the highest NO2 and O3 concentrations, thus increasing the range of values across the city. However, the sensors suggest a good performance with respect to capturing the spatial variability in NO2 and O3 and are very convenient to use, having great potential for capturing temporal variability.

Unlabelled: A single event-multilevel surgery (SEMLS) is today a well-established modality of treatment in children with cerebral palsy (CP). It comprises muscle lengthening/transfers and correction of bony deformities in a single surgical session. Functional improvements after SEMLS have been examined thoroughly, however little is known about the impact of SEMLS on the quality of life (QOL) of children with CP. This study reports on the QOL of children/adolescents with CP after SEMLS. Forty patients underwent SEMLS and were classified according GMFCS levels II-V, age and time span between surgery and questioning. The Cerebral Palsy Quality of Life Questionnaire for Children (CP QOL-Child) and an author developed questionnaire were completed to evaluate QOL. Overall, children/adolescents reported high quality of life scores after SEMLS on the CP QOL-Child. For all the domains of the CP QOL-Child the children reported significant higher scores than their parents (p < 0.05). Significant differences (p < 0.05) were found for the functional-related domains of the CP QOL-Child between GMFCS level III and levels IV-V, but not for the socio-emotional domains. Older children at the moment of surgery (15y0m-18y11m) reported significantly less 'pain and feeling about disability' than children who were younger when operated on (10y0m-14y11m). Almost all aspects included in the author developed questionnaire improved for the majority of the children after SEMLS., Conclusion: After SEMLS, children with CP report high quality of life, significantly higher than their parents perceived. Function and age may influence specific aspects of QOL after SEMLS., (Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)