The first skeletal evidence of an Upper Triassic (Rhaetian) diapsid reptile from the Western Carpathians (Str\ue1\u17eov Highlands, Slovakia)

Here we describe the first skeletal evidence of a tetrapod from Rhaetian (Upper Triassic) marine deposits of the Western Carpathians. The material consists of an isolated left femur and comes from the abo\u10dka locality near \u10ci\u10dmany in the Str\ue1\u17eov Highlands. Based on morphological, histological, and stratigraphic evidence, we can exclude affinities of this femur to the most commonly occurring aquatic reptiles: the Eosauropterygia. The histology of a femur of aff. Pachystropheus from Aust Cliff, Gloucestershire, UK, is also described here for the first time and compared to the bone from Slovakia. However, a precise taxonomical assignment of the Rhaetian femur from Slovakia is not possible. The bone shows strong osteosclerosis that points to an inhabitant of a shallow marine environment. On the basis of morphological and histological characters, affinities to a cyamodontoid placodont, Endennasaurus-like thalattosaur or a rhynchocephalian are conceivable. The morphology of the Slovak find does not fully exclude choristoderan affinity, but the rare histological data available for comparison do not support such a statement. For all these reasons, we allocated this bone as Diapsida indet. The bone described here sheds the first, although limited light on the possible faunal composition of the Rhaetian tetrapod assemblage in the Western Carpathians. We can assume that the bone, which shows marks of transport, either represents an allochthonous component in this marine environment, transported postmortem and most likely from nearby dry land (i.e., in the case of rhynchocephalian affinities), or it belonged to an inhabitant of this shallow coastal biotope (e.g., cyamodontoid placodont affinities)

Association of ataxin-7 with the proteasome subunit S4 of the 19S regulatory complex

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by ataxia and selective neuronal cell loss caused by the expansion of a translated CAG repeat encoding a polyglutamine tract in ataxin-7, the SCA7 gene product. To gain insight into ataxin-7 function and to decipher the molecular mechanisms of neurodegeneration in SCA7, a two-hybrid assay was performed to identify ataxin-7 interacting proteins. Herein, we show that ataxin-7 interacts with the ATPase subunit S4 of the proteasomal 19S regulatory complex. The ataxin-7/S4 association is modulated by the length of the polyglutamine tract whereby S4 shows a stronger association with the wild-type allele of ataxin-7. We demonstrate that endogenous ataxin-7 localizes to discrete nuclear foci that also contain additional components of the proteasomal complex. Immunohistochemical analyses suggest alterations either of the distribution or the levels of S4 immunoreactivity in neurons that degenerate in SCA7 brains. Immunoblot analyses demonstrate reduced levels of S4 in SCA7 cerebella without evident alterations in the levels of other proteasome subunits. These results suggest a role for S4 and ubiquitin-mediated proteasomal proteolysis in the molecular pathogenesis of SCA7

Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy

Distal hereditary motor neuropathies are pure motor disorders of the peripheral nervous system resulting in severe atrophy and wasting of distal limb muscles. In two pedigrees with distal hereditary motor neuropathy type II linked to chromosome 12q24.3, we identified the same mutation (K141N) in small heat-shock 22-kDa protein 8 (encoded by HSPB8; also called HSP22). We found a second mutation (K141E) in two smaller families. Both mutations target the same amino acid, which is essential to the structural and functional integrity of the small heat-shock protein alphaA-crystallin. This positively charged residue, when mutated in other small heat-shock proteins, results in various human disorders. Coimmunoprecipitation experiments showed greater binding of both HSPB8 mutants to the interacting partner HSPB1. Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders