IMPDH2 : a new gene associated with dominant juvenile-onset dystonia-tremor disorder

The aetiology of dystonia disorders is complex, and next-generation sequencing has become a useful tool in elucidating the variable genetic background of these diseases. Here we report a deleterious heterozygous truncating variant in the inosine monophosphate dehydrogenase gene (IMPDH2) by whole-exome sequencing, co-segregating with a dominantly inherited dystonia-tremor disease in a large Finnish family. We show that the defect results in degradation of the gene product, causing IMPDH2 deficiency in patient cells. IMPDH2 is the first and rate-limiting enzyme in the de novo biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders. We report IMPDH2 as a new gene to the dystonia disease entity. The evidence underlines the important link between guanine metabolism, dopamine biosynthesis and dystonia.Peer reviewe

Hydrophobin Film Structure for HFBI and HFBII and Mechanism for Accelerated Film Formation

Peer reviewe

Correlating charge transport to structure in deconstructed diketopyrrolopyrrole oligomers: A case study of a monomer in field-effect transistors

Copolymers based on diketopyrrolopyrrole (DPP) cores have attracted a lot of attention because of their high p-type as well as n-type carrier mobilities in organic field-effect transistors (FETs) and high power conversion efficiencies in solar cell structures. We report the structural and charge transport properties of n-dialkyl side-chain-substituted thiophene DPP end-capped with a phenyl group (Ph-TDPP-Ph) monomer in FETs which were fabricated by vacuum deposition and solvent coating. Grazing-incidence X-ray diffraction (GIXRD) from bottom-gate, bottom-contact FET architectures was measured with and without biasing. Ph-TDPP-Ph reveals a polymorphic structure with pi-conjugated stacking direction oriented in-plane. The unit cell comprises either one monomer with a = 20.89 angstrom, b = 13.02 angstrom, c = 5.85 angstrom, alpha = 101.4 degrees, beta = 90.6 degrees, and gamma = 94.7 degrees for one phase (TR1) or two monomers with a = 24.92 angstrom, b = 25.59 angstrom, c = 5.42 angstrom, alpha = 80.3 degrees, beta = 83.5 degrees, and gamma = 111.8 degrees for the second phase (TR2). The TR2 phase thus signals a shift from a coplanar to herringbone orientation of the molecules. The device performance is sensitive to the ratio of the two triclinic phases found in the film. Some of the best FET performances with p-type carrier mobilities of 0.1 cm(2)/V s and an on/off ratio of 10(6)are for films that comprise mainly the TR1 phase. GIXRD from in operando FETs demonstrates the crystalline stability of Ph-TDPP-Ph

Aggregation and self-assembly of hydrophobins from Trichoderma reesei: low-resolution structural models.

Hydrophobins are secreted fungal proteins, which have diverse roles in fungal growth and development. They lower the surface tension of water, work as adhesive agents and coatings, and function through self-assembly. One of the characteristic properties of hydrophobins is their tendency to form fibrillar or rod-like aggregates at interfaces. Their structure is still poorly known. In a step to elucidate the structure/function relation of hydrophobin self-assembly, we present the low-resolution structure of self-assembled fibrils of the class II hydrophobin HFBII from Trichoderma reesei based on small and wide-angle x-ray scattering. We first studied the solution state (10 mg/mL) of both HFBI and HFBII and showed that they formed assemblages in aqueous solution, which have a radius of gyration of ~24 A and maximum dimension of ~65 A, corresponding to the size of a tetramer. This result was supported by size-exclusion chromatography. Undried samples of HFBII fibrils had a monoclinic crystalline structure, which changed to hexagonal when the material was dried. A low-resolution structure for the HFBII fibrils is suggested. There are data in the literature based on staining properties suggesting that hydrophobins of class I form assemblies with an amyloid structure. Comparison of the HFBII data (x-ray results, staining with thioflavin T) to published data showed that the HFBII assemblages are not amyloid