Byström, A. | Search bioRxiv

bioRxiv2019

Range of motion and between-measurement variation of spinal kinematics in sound horses at trot on the straight line and on the lunge.

Clinical assessment of spinal motion in horses is part of many routine clinical exams but remains highly subjective. A prerequisite for the quantification is the assessment of the expected normal range of motion and variability of back kinematics. The aim of this study was to objectively quantify spinal kinematics and between-measurement, -surface and -day variation in owner-sound horses. In an observational study, twelve owner-sound horses were trotted 12 times on four different paths (hard/soft straight line, soft lunge left and right). Measurements were divided over three days, with five repetitions on day one and two, and two repetitions on day three (recheck) which occurred 28-55 days later. Optical motion capture was used to collect kinematic data. Elements of the outcome were: 1) Ranges of Motion (ROM) with confidence intervals per path and surface, 2) a variability model to calculate between-measurement variation and test the effect of time, surface and path, 3) intraclass correlation coefficients (ICC) to determine repeatability. ROM was lowest on the hard straight line. Cervical lateral bending was doubled on the left compared to the right lunge. Mean variation for the flexion-extension and lateral bending of the whole back were 0.8 and 1 degrees. Pelvic motion showed a variation of 1.0 (pitch), 0.7 (yaw) and 1.3 (roll) degrees. For these five parameters, a tendency for more variation on the hard surface and reduced variation with increased repetitions was observed. More variation was seen on the recheck (p<0.001). ICC values for the pelvis were between 0.76 and 0.93, for the whole back flexion-extension and lateral bending between 0.51 and 0.91. Between-horse variation was substantially higher than within-horse variation. Concluding, ROM and variation in spinal biomechanics are horse-specific and small, necessitating individual analysis and making subjective clinical assessment of spinal kinematics challenging.

bioengineering↗

bioRxiv2019

SSD1 suppresses phenotypes induced by the lack of Elongator-dependent tRNA modifications

The Elongator complex promotes formation of 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side-chains on uridines at the wobble position of cytosolic eukaryotic tRNAs. In all eukaryotic organisms tested to date, the inactivation of Elongator not only leads to the lack of mcm5/ncm5 groups in tRNAs, but also a wide variety of phenotypes. Although the phenotypes are most likely caused by a translational defect induced by reduced functionality of the hypomodified tRNAs, the mechanism(s) underlying individual phenotypes are poorly understood. In this study, we show that the genetic background modulates the phenotypes induced by the lack of mcm5/ncm5 groups in Saccharomyces cerevisiae. We show that the stress-induced growth defects of Elongator mutants are stronger in the W303 than in the closely related S288C genetic background and that the phenotypic differences are caused by the known polymorphism at the locus for the mRNA binding protein Ssd1. Moreover, the mutant ssd1 allele found in W303 cells is required for the reported histone H3 acetylation and telomeric gene silencing defects of Elongator mutants. The difference at the SSD1 locus also partially explains why the simultaneous lack of mcm5 and 2-thio groups at wobble uridines is lethal in the W303 but not in the S288C background. Collectively, our results demonstrate that the SSD1 locus modulates phenotypes induced by the lack of Elongator-dependent tRNA modifications. Author SummaryModified nucleosides in the anticodon region of tRNAs are important for the efficiency and fidelity of translation. The Elongator complex promotes formation of several related modified uridine residues at the wobble position of eukaryotic tRNAs. In yeast, plants, worms, mice and humans, mutations in genes for Elongator subunits lead to a wide variety of different phenotypes. Here, we show that the genetic background modulates the phenotypic consequences of the inactivation of budding yeast Elongator. This background effect is largely a consequence of a polymorphism at the SSD1 locus, encoding a RNA binding protein that influences translation, stability and/or localization of mRNAs. We show that several phenotypes reported for yeast Elongator mutants are either significantly stronger or only detectable in strains harboring a mutant ssd1 allele. Thus, SSD1 is a suppressor of the phenotypes induced by the hypomodification of tRNAs.

genetics↗