De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals where it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologs. Using RNA-sequencing, we show how 5’ splice site usage is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 bp region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide

Laboratory studies of astrophysical molecules: a new UCL apparatus

Topics that are covered include electron scattering in the scanning TEM; basic theory of inelastic electron imaging; study of confined atoms by electron excitation; helium bubbles created in extreme pressure with application to nuclear safety; lithium ion implantation; electron and positron scattering from clusters; electron scattering from physi- and chemi-absorbed molecules on surfaces; coincidence studies; electron scattering from biological molecules; electron spectroscopy as a tool for environmental science; electron scattering in the presence of intense fields; electron scattering from astrophysical molecules; electon interatctions an detection of x-ray radiation

VUV photoabsorption spectroscopy of sulfur dioxide ice

In this paper we present the first study of the VUV photoabsorption spectrum of condensed phase SO2 recorded over the VUV region 120 to 320 nm (10.33 to 3.64 eV). Distinct spectral features were observed that can be used to distinguish between the formation of amorphous and crystalline ice structures. These signatures may then be used to probe the formation of different ice structures as a function of both deposition rate and substrate temperature

Atmospheric chemistry with synchrotron radiation

Synchrotron radiation is a good mimic of solar radiation and therefore has been widely used to study photo-induced physics and chemistry in the terrestrial atmosphere. In this paper we review how synchrotron radiation is being used as a tool for investigating atmospheric physics and chemistry with particular emphasis on studies related to ozone depletion, global warming and ionospheric phenomena. The paper concludes with a discussion of the new possibilities that the next generation of synchrotron-based light sources will provide

The site-specificity of supragingival calculus deposition on the lingual surfaces of the six permanent lower anterior teeth in humans and the effects of age, sex, gum-chewing habits, and the time since the last prophylaxis on calculus scores

The hypotheses to be tested were: (i) that chewing sugar-free gum frequently and for long periods would be associated with higher amounts of supragingival calculus, and (ii) that there would be no site-specificity of calculus deposition on the lingual surfaces of the 6 lower anterior teeth. Subjects, 436 in Glasgow and 191 in Winnipeg, were scored for calculus at mesial, lingual, and distal sites on the lingual surface of each of the 6 lower anterior teeth, by the Volpe-Manhold method. They also answered questions on the time since the last prophylaxis, the frequency of gum chewing, the type of gum chewed, and the length of a typical gum-chewing episode. A subset (233) of the Glasgow subjects were scaled and re-scored for calculus 3 months later. When the data for the logarithmic transformations of the initial calculus scores were subjected to stepwise multiple-regression analysis, the only factor which correlated significantly with initial calculus scores in both cities was the time since the last prophylaxis. In the Glasgow subjects scored 3 months after a prophylaxis, there was a negative correlation between chewing sugar-free gum and calculus scores, whereas in the Winnipeg subjects, age and the chewing of sucrose-containing and sugar-free gum were positively correlated with calculus scores. Thus, the results were contradictory with respect to the first-tested hypothesis. The calculus distribution patterns were very similar in the subset of Glasgow subjects and the Winnipeg subjects, with the amounts on the lateral incisors and canines averaging 70.2% and 44.5%, respectively, of those on the central incisors. Thus, the second hypothesis was disproved

Temperature dependent high-resolution infrared photoabsorption cross-sections of trifluoromethyl sulphur pentafluoride

Absolute infrared photoabsorption cross-sections have been measured over the range 600-1500 cm(-1) for the powerful greenhouse gas SF5CF3 at high resolution (0.03 cm(-1)) and at temperatures between 203 and 298 K. Our data indicate that the integrated absorption intensity shows a weak negative dependence on temperature. It is concluded therefore that previous calculations of radiative forcings and global warming potentials based on room-temperature data are reasonable estimates for the atmosphere, but may be low by a few percent. (C) 2002 Elsevier Science B.V. All rights reserved