Functional MRI, voxel based morphometry, and diffusion-tensor imaging showed these cerebellar alterations as being of functional and structural nature.”
“Microtubules are highly dynamic alpha beta-tubulin polymers. In vitro and in living cells, microtubules are most often cold-and nocodazole-sensitive. When present, the MAP6/STOP family of proteins protects microtubules from cold-and nocodazole-induced depolymerization but the molecular and structure determinants by which these proteins stabilize microtubules remain under debate. We show here that a short protein fragment

from MAP6-N, which encompasses its Mn1 and Mn2 modules (MAP6(90-177)), recapitulates the function of the full-length MAP6-N protein toward microtubules, i.e. its ability Silmitasertib to stabilize microtubules in vitro and in cultured cells in ice-cold conditions or in the presence of nocodazole. We further show for the first time, using biochemical assays and NMR spectroscopy, that these Natural Product Library order effects result from the binding of MAP6(90-177) to microtubules with a 1:1 MAP6(90-177): tubulin heterodimer

stoichiometry. NMR data demonstrate that the binding of MAP6(90-177) to microtubules involve its two Mn modules but that a single one is also able to interact with microtubules in a closely similar manner. This suggests that the Mn modules represent each a full microtubule binding domain and that MAP6 proteins may stabilize microtubules by bridging tubulin heterodimers from adjacent protofilaments or within small molecule library screening a protofilament. Finally,

we demonstrate that Ca2+-calmodulin competes with microtubules for MAP6(90-177) binding and that the binding mode of MAP6(90-177) to microtubules and Ca2+-calmodulin involves a common stretch of amino acid residues on the MAP6(90-177) side. This result accounts for the regulation of microtubule stability in cold condition by Ca2+-calmodulin.”
“Background: Sequence variants in coding and non-coding regions of THAP1 have been associated with primary dystonia.\n\nMethods: In this study, 1,446 Caucasian subjects with mainly adult-onset primary dystonia and 1,520 controls were genotyped for a variant located in the 5′-untranslated region of THAP1 (c.-237_236GA>TT).\n\nResults: Minor allele frequencies were 62/2892 (2.14%) and 55/3040 (1.81%) in subjects with dystonia and controls, respectively (P=0.202). Subgroup analyses by gender and anatomical distribution also failed to attain statistical significance. In addition, there was no effect of the TT variant on expression levels of THAP1 transcript or protein.\n\nDiscussion: Our findings indicate that the c.-237_236GA>TT THAP1 sequence variant does not increase risk for adult-onset primary dystonia in Caucasians.