How long is too long? Effects of loop size on G-quadruplex stability

We compared here 80 different sequences containing four tracts of three guanines with loops of variable length (between 1 and 15 bases for unmodified sequences, up to 30 for fluorescently labeled oligonucleotides). All sequences were capable of forming stable quadruplexes, with T_m above physiological temperature in most cases. Unsurprisingly, the melting temperature was systematically lower in sodium than in potassium but the difference between both ionic conditions varied between 1 and >39°C (average difference: 18.3°C). Depending on the sequence context, and especially for G4 sequences involving two very short loops, the third one may be very long without compromising the stability of the quadruplex. A strong inverse correlation between total loop length and T_m was found in K⁺: each added base leads to a 2°C drop in T_m or ∼0.3 kcal/mol loss in ΔG°. The trend was less clear in Na⁺, with a longer than expected optimal loop length (up to 5 nt). This study will therefore extend the sequence repertoire of quadruplex-prone sequences, arguing for a modification of the widely used consensus (maximal loop size of 7 bases).     

Insulin dependent diabetes in childhood and material deprivation in northern England, 1977-86.

OBJECTIVE--To determine the incidence of insulin dependent diabetes in the Northern region of England in children less than 16 years old in the period 1977 to 1986 and to relate the incidence data to an index of deprivation. DESIGN--Retrospective analysis of hospital case records identified from the regional health authority''s computer; validation of the primary source with hospital clinic registers and community paediatric registers. SETTING--Northern region, excluding South Cumbria District Health Authority (659,300 children under 16 in 1981). PATIENTS--All children diagnosed with insulin dependent diabetes before the age of 16 and resident in the region at time of diagnosis. MAIN OUTCOME MEASURES--Incidence rates for the 10 year period and analysis of incidence rates within categories of deprivation. RESULTS--919 incident cases were identified. The validation procedure covered 54% of all cases identified and gave 95% completeness of ascertainment. The average annual incidence over the 10 year period was 14.8/100,000 for girls and 13.4/100,000 for boys. The annual incidence for the most and least deprived areas of the region was 18.7/100,000 (95% confidence interval 16.2 to 21.5) for boys and 7/100,000 (5.6 to 8.8) for girls. There was a highly significant trend (p less than 0.001) of decreasing incidence with decreasing level of deprivation. CONCLUSIONS--In the north of England the incidence of childhood diabetes is related to material deprivation.