Long-term survival for a cohort of adults with cerebral palsy

The aim of this study was to investigate long-term survival and examine causes of death in adult patients with cerebral palsy (CP). A 1940–1950 birth cohort based on paediatric case referral allows for long-term survival follow-up. Survival is analyzed by birth characteristics and severity of disability from age 20 years (and age 2y for a subset of the data). Survival outcome compared with that expected in the general population based on English life tables. The main cohort consisted of 341 individuals, with 193 males and 148 females. Conditional on surviving to age 20 years, almost 85% of the cohort survived to age 50 years (a comparable estimate for the general population is 96%). Very few deaths were attributed to CP for those people dying over 20 years of age. Females survived better than males. However, females faced a greater increase in risk relative to the general population than did males. We conclude that survival outlook is good though lower than in the general population. The relative risk of death compared with the UK population decreases with age, although it shows some indication of rising again after age 50 years. Many more deaths were caused by diseases of the respiratory system among those dying in their 20s and 30s than would be expected in the general population. Many fewer deaths than expected in this age group are caused by injuries and accidents. For those people who die in their 40s and 50s, an increase in deaths due to diseases of the circulatory system and neoplasms is observed. More deaths than expected in this age group are due to diseases of the nervous system

Rlp7p is associated with 60S preribosomes, restricted to the granular component of the nucleolus, and required for pre-rRNA processing

Many analyses have examined subnucleolar structures in eukaryotic cells, but the relationship between morphological structures, pre-rRNA processing, and ribosomal particle assembly has remained unclear. Using a visual assay for export of the 60S ribosomal subunit, we isolated a ts-lethal mutation, rix9-1, which causes nucleolar accumulation of an Rpl25p-eGFP reporter construct. The mutation results in a single amino acid substitution (F(176)S) in Rlp7p, an essential nucleolar protein related to ribosomal protein Rpl7p. The rix9-1 (rlp7-1) mutation blocks the late pre-RNA cleavage at site C(2) in ITS2, which separates the precursors to the 5.8S and 25S rRNAs. Consistent with this, synthesis of the mature 5.8S and 25S rRNAs was blocked in the rlp7-1 strain at nonpermissive temperature, whereas 18S rRNA synthesis continued. Moreover, pre-rRNA containing ITS2 accumulates in the nucleolus of rix9-1 cells as revealed by in situ hybridization. Finally, tagged Rlp7p was shown to associate with a pre-60S particle, and fluorescence microscopy and immuno-EM localized Rlp7p to a subregion of the nucleolus, which could be the granular component (GC). All together, these data suggest that pre-rRNA cleavage at site C(2) specifically requires Rlp7p and occurs within pre-60S particles located in the GC region of the nucleolus

124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics

Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes.We thank Martin Spitaler and the imaging facility of the MPI of Biochemistry for confocal imaging support

The X-ray Spectral Properties and Variability of Luminous High-Redshift Active Galactic Nuclei

We perform a detailed investigation of moderate-to-high quality X-ray spectra of ten of the most luminous active galactic nuclei (AGNs) known at z>4 (up to z~6.28). This study includes five new XMM observations and five archived X-ray observations (four by XMM and one by Chandra). We find that the X-ray power-law photon indices of our sample, composed of eight radio-quiet sources and two that are moderately radio loud, are not significantly different from those of lower redshift AGNs. The upper limits obtained on intrinsic neutral hydrogen column densities, N_H<~10^{22}-10^{23} cm^{-2}, indicate that these AGNs are not significantly absorbed. A joint fit performed on our eight radio-quiet sources, with a total of ~7000 photons, constrains the mean photon index of z>4 radio-quiet AGNs to Gamma=1.97^{+0.06}_{-0.04}, with no detectable intrinsic dispersion from source to source. We also obtain a strong constraint on the mean intrinsic column density, N_H<~3x10^{21} cm^{-2}, showing that optically selected radio-quiet AGNs at z>4 are, on average, not more absorbed than their lower-redshift counterparts. All this suggests that the X-ray production mechanism and the central environment in radio-quiet AGNs have not significantly evolved over cosmic time. The mean equivalent width of a putative neutral narrow Fe Ka line is constrained to be <~190 eV, and similarly we place constraints on the mean Compton reflection component (R<~1.2). None of the AGNs varied on short (~1 hr) timescales, but on longer timescales (months-to-years) strong variability is observed in four of the sources. In particular, the X-ray flux of the z=5.41 radio-quiet AGN SDSS 0231-0728 dropped by a factor of ~4 over a rest-frame period of 73 d. This is the most extreme X-ray variation observed in a luminous z>4 radio-quiet AGN.Comment: 10 pages (emulateapj), 5 figures. Accepted by Ap