Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders, caused or modified by an unstable CAG-repeat expansion in the SCA2 gene, which encodes a polyglutamine (polyQ) domain expansion in ataxin-2 (ATXN2). ATXN2 is an RNA-binding protein and interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum. Under cell stress, ATXN2, PABPC1 and small ribosomal subunits are relocated to stress granules, where mRNAs are protected from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates RNA processing. Here, we investigated the RNA profile of the liver and cerebellum from Atxn2 knockout (Atxn2−/−) mice at two adult ages, employing oligonucleotide microarrays. Prominent increases were observed for Lsm12/Paip1 (>2-fold), translation modulators known as protein interactor/competitor of ATXN2 and for Plin3/Mttp (>1.3-fold), known as apolipoprotein modulators in agreement with the hepatosteatosis phenotype of the Atxn2−/− mice. Consistent modest upregulations were also observed for many factors in the ribosome and the translation/secretion apparatus. Quantitative reverse transcriptase PCR in liver tissue validated >1.2-fold upregulations for the ribosomal biogenesis modulator Nop10, the ribosomal components Rps10, Rps18, Rpl14, Rpl18, Gnb2l1, the translation initiation factors Eif2s2, Eif3s6, Eif4b, Pabpc1 and the rER translocase factors Srp14, Ssr1, Sec61b. Quantitative immunoblots substantiated the increased abundance of NOP10, RPS3, RPS6, RPS10, RPS18, GNB2L1 in SDS protein fractions, and of PABPC1. In mouse embryonal fibroblasts, ATXN2 absence also enhanced phosphorylation of the ribosomal protein S6 during growth stimulation, while impairing the rate of overall protein synthesis rates, suggesting a block between the enhanced translation drive and the impaired execution. Thus, the physiological role of ATXN2 subtly modifies the abundance of cellular translation factors as well as global translation.Electronic supplementary materialThe online version of this article (doi:10.1007/s10048-015-0441-5) contains supplementary material, which is available to authorized users.

The reference ranges for blood flow velocities and resistance indices in the umbilical artery calculated by the authors serve as the basis for Doppler ultrasound antenatal examinations in a normal patient population and enable the early diagnosis of fetal risk.

The goal of the present study was to establish new Doppler reference ranges for maternal heart rate, intensity-weighted mean blood flow velocities (Vmean) and impedance indices (PI, RI) for the uterine artery by automated waveform analysis. Materials and Methods: A cross-sectional prospective study of 921 low-risk pregnancies was performed at 18 -42 weeks of gestation. Uterine blood flow velocities were derived with pulsedwave color Doppler. Measurements were carried out 1 to 2 cm above the crossing of the uterine and external iliac arteries. Reference ranges for the individual measuring parameters were constructed based on a growth function from a fourparameter class of monotonic continuous functions according to the smallest square principle. Results: A significant increase in intensityweighted mean uterine blood flow velocities was observed at 18 -42 weeks of gestation (Vmean = 43 cm/s to 50 cm/s (p < 0.001)). Reference curves for the pulsatility and resistance indices (PI, RI) significantly decreased with progressing gestation (PI: 18 weeks: 0.89; 42 weeks: 0.65 and RI: 18 weeks: 0.45; 42 weeks: 0.35). No significant PI and RI differences were observed when different placental locations were compared. The maternal heart rate decreased from 88 bpm to 77 bpm. Conclusion: Normal ranges for blood flow velocities and impedance indices in the uterine artery were established by Doppler ultrasound antenatal examinations of a large population of low-risk pregnancies. The data are proposed as reference curves to allow the early diagnosis of maternal and fetal risks.

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The ranges for blood flow velocities and impedance indices in the fetal pulmonary artery calculated by the authors may serve as reference values to help distinguish a normal patient population from patients carrying fetuses at high risk for neonatal lung disease in antenatal examinations.

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