The third dimension of scoliosis: The forgotten axial plane

Idiopathic scoliosis is a three-dimensional (3D) deformity of the spine. In clinical practice, however, the diagnosis and treatment of scoliosis consider only two dimensions (2D) as they rely solely on postero-anterior (PA) and lateral radiographs. Thus, the projections of the deformity are evaluated in only the coronal and sagittal planes, whereas those in the axial plane are disregarded, precluding an accurate assessment of the 3D deformity. A universal dogma in engineering is that designing a 3D object requires drawing projections of the object in all three planes. Similarly, when dealing with a 3D deformity, knowledge of the abnormalities in all three planes is crucial, as each plane is as important as the other two planes. This article reviews the chronological development of axial plane imaging and spinal deformity measurement

Axial plane dissimilarities of two identical Lenke-type 6C scoliosis cases visualized and analyzed by vertebral vectors

Purpose The global appearance of scoliosis in the horizontal plane is not really known. Therefore, the aims of this study were to analyze scoliosis in the horizontal plane using vertebral vectors in two patients classified with the same Lenke group, and to highlight the importance of the information obtained from these vertebral vector-based top-view images in clinical practice. Methods Two identical cases of scoliosis were selected, based on preoperative full-body standing anteroposterior and lateral radiographs obtained by the EOS™ 2D/3D system. Three-dimensional (3D) surface reconstructions of the spinal curves were performed by using sterEOS™ 3D software before and after surgery. In both patients, we also determined the vertebral vectors and horizontal plane coordinates for analyzing the curves mathematically before and after surgery. Results Despite the identical appearance of spinal curves in the frontal and sagittal planes, the horizontal views seemed to be significantly different. The vertebral vectors in the horizontal plane provided different types of parameters regarding scoliosis and the impact of surgical treatment: reducing lateral deviations, achieving harmony of the curves in the sagittal plane, and reducing rotations in the horizontal plane. Conclusions Vertebral vectors allow the evolution of scoliosis curve projections in the horizontal plane before and after surgical treatment, along with representation of the entire spine. The top view in the horizontal plane is essential to completely evaluate the scoliosis curves, because, despite the similar representations in the frontal and sagittal planes, the occurrence of scoliosis in the horizontal plane can be completely different.There is no funding source

The horizontal plane appearances of scoliosis: what information can be obtained from top-view images?

PURPOSE: A posterior-anterior vertebral vector is proposed to facilitate visualization and understanding of scoliosis. The aim of this study was to highlight the interest of using vertebral vectors, especially in the horizontal plane, in clinical practice. METHODS: We used an EOS two-/three-dimensional (2D/3D) system and its sterEOS 3D software for 3D reconstruction of 139 normal and 814 scoliotic spines-of which 95 cases were analyzed pre-operatively and post-operatively, as well. Vertebral vectors were generated for each case. Vertebral vectors have starting points in the middle of the interpedicular segment, while they are parallel to the upper plate, ending in the middle of the segment joining the anterior end plates points, thus defining the posterior-anterior axis of vertebrae. To illustrate what information could be obtained from vertebral vector-based top-view images, representative cases of a normal spine and a thoracic scoliosis are presented. RESULTS: For a normal spine, vector projections in the transverse plane are aligned with the posterior-anterior anatomical axis. For a scoliotic spine, vector projections in the horizontal plane provide information on the lateral decompensation of the spine and the lateral displacement of vertebrae. In the horizontal plane view, vertebral rotation and projections of the sagittal curves can also be analyzed simultaneously. CONCLUSIONS: The use of posterior-anterior vertebral vector facilitates the understanding of the 3D nature of scoliosis. The approach used is simple. These results are sufficient for a first visual analysis furnishing significant clinical information in all three anatomical planes. This visualization represents a reasonable compromise between mathematical purity and practical use

SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression

The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1/2

Hepatocyte nuclear factor 4 alpha (HNF4alpha) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4alpha is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4alpha. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4alpha. However, based on our previous results we hypothesized that HNF4alpha is also regulated at the post-transcriptional level by ERK1/2. Here we show that ERK1/2 is capable of directly phosphorylating HNF4alpha in vitro at several phosphorylation sites including residues previously shown to be targeted by other kinases, as well. Furthermore, we also demonstrate that phosphorylation of HNF4alpha leads to a reduced trans-activational capacity of the nuclear receptor in luciferase reporter gene assay. We confirm the functional relevance of these findings by demonstrating with ChIP-qPCR experiments that 30-minute activation of ERK1/2 leads to reduced chromatin binding of HNF4alpha. Accordingly, we have observed decreasing but not disappearing binding of HNF4alpha to the target genes. In addition, 24-hour activation of the pathway further decreased HNF4alpha chromatin binding to specific loci in ChIP-qPCR experiments, which confirms the previous reports on the decreased expression of the HNF4a gene due to ERK1/2 activation. Our data suggest that the ERK1/2 pathway plays an important role in the regulation of HNF4alpha-dependent hepatic gene expression