The nine-amino-acid activation domain (9aaTAD) is defined by a short amino acid pattern including two hydrophobic regions (positions p3-4 and p6-7). The KIX domain of mediator transcription CBP interacts with the 9aaTAD domains of transcription factors MLL, E2A, NF-kB, and p53. In this study, we analyzed the 9aaTADs-KIX interactions by nuclear magnetic resonance. The positions of three KIX helixes α1-α2-α3 are influenced by sterically-associated hydrophobic I611, L628, and I660 residues that are exposed to solvent. The positions of two rigid KIX helixes α1 and α2 generate conditions for structural folding in the flexible KIX-L12-G2 regions localized between them. The three KIX I611, L628, and I660 residues interact with two 9aaTAD hydrophobic residues in positions p3 and p4 and together build a hydrophobic core of five residues (5R). Numerous residues in 9aaTAD position p3 and p4 could provide this interaction. Following binding of the 9aaTAD to KIX, the hydrophobic I611, L628, and I660 residues are no longer exposed to solvent and their position changes inside the hydrophobic core together with position of KIX α1-α2-α3 helixes. The new positions of the KIX helixes α1 and α2 allow the KIX-L12-G2 enhanced formation. The second hydrophobic region of the 9aaTAD (positions p6 and p7) provides strong binding with the KIX-L12-G2 region. Similarly, multiple residues in 9aaTAD position p6 and p7 could provide this interaction. In conclusion, both 9aaTAD regions p3, p4 and p6, p7 provide co-operative and highly universal binding to mediator KIX. The hydrophobic core 5R formation allows new positions of the rigid KIX α-helixes and enables the enhanced formation of the KIX-L12-G2 region. This contributes to free energy and is the key for the KIX-9aaTAD binding. Therefore, the 9aaTAD-KIX interactions do not operate under the rigid key-and-lock mechanism what explains the 9aaTAD natural variability.
There are significant morphologic changes in spinal autonomic nervous structures in scoliotic patients. These findings can help us in the search for the etiology of scoliosis.
The involvement of the brain motor system in idiopathic scoliosis remains unclear. In this paper, we question whether the functional connectivity (FC) of the central motor circuitry is abnormal in adolescent idiopathic scoliosis (AIS) and whether it can be modified by flexion of the lower extremities. Functional magnetic resonance imaging (fMRI) in 18 patients with a right thoracic idiopathic curve greater than 30° (mean angle 49.4°, mean age 15.3 years, 4 males) and 22 healthy controls (mean age 18.2 years, 4 males) was explored using a 3T MR scanner. We measured their resting-state fMRI: a) with extended lower extremities; b) with semiflexion of the left lower extremity and extended right lower extremity, with hip abduction. Decreased FC between the secondary motor area (SMA) and postcentral cortex, pallidum and cuneus, postcentral gyrus and cerebellum, putamen and temporal lateral neocortex was observed in AIS. This pathological connectivity was reversed by lower extremity semiflexion. The FC between cortical and subcortical motor structures is significantly decreased in AIS. The decreased FC of the SMA, basal ganglia, cuneus (a hub structure), and cerebellum indicates the functional impairment of structures involved in regulating muscular tone. FC impairment in patients with AIS appears to be a reaction to the pathological condition. This pathological pattern flexibly reacts to changes in the positioning of the lower extremities, showing that the functional impairment of brain motor circuitry in AIS is reversible. We suggest that the reactivity of cerebral activity leading to brain activity normalization could be used for a rehabilitation program for patients with AIS.
PURPOSE OF THE STUDYThe aim of this retrospective study was to present a comprehensive overview of the causes of bone-tendon-bone (BTB) autograft failure after primary anterior cruciate ligament (ACL) reconstruction.
MATERIAL AnD METHODSBetween 2003 and 2013, we performed revision ACL replacement in 47 patients who had undergone primary BTB autograft ACL reconstruction in other hospitals. The group consisted of 16 women (aged 25 to 48 years) and 31 men (25 to 46 years). Surgery was performed on the right knee in 26 and on the left knee in 21 patients.
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