Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results.

Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells.

Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+ unfoldase.

The 26S proteasome is the major eukaryotic ATP-dependent protease, yet the detailed mechanisms used by the proteasomal heterohexameric AAA+ unfoldase to drive substrate degradation remain poorly understood. To perform systematic mutational analyses of individual ATPase subunits, we heterologously expressed the unfoldase subcomplex from Saccharomyces cerevisiae in Escherichia coli and reconstituted the proteasome in vitro. Our studies demonstrate that the six ATPases have distinct roles in degradation, corresponding to their positions in the spiral staircases adopted by the AAA+ domains in the absence or presence of substrate.

Formation of an intricate helical bundle dictates the assembly of the 26S proteasome lid.

The 26S proteasome is the major ATP-dependent protease in eukaryotes and thus involved in regulating a diverse array of vital cellular processes. Three subcomplexes form this massive degradation machine: the lid, the base, and the core. While assembly of base and core has been well-studied, the detailed molecular mechanisms involved in formation of the nine-subunit lid remain largely unknown.

Complete subunit architecture of the proteasome regulatory particle.

The proteasome is the major ATP-dependent protease in eukaryotic cells, but limited structural information restricts a mechanistic understanding of its activities. The proteasome regulatory particle, consisting of the lid and base subcomplexes, recognizes and processes polyubiquitinated substrates. Here we used electron microscopy and a new heterologous expression system for the lid to delineate the complete subunit architecture of the regulatory particle from yeast.

Osseous regeneration after therapy in patients with head and neck tumors.

Four patients with head and neck tumors were observed by serial computed tomography (CT) during treatment. Osseous regeneration was demonstrated at sites of initial osteolytic destruction in two patients who responded to therapy. This regeneration was observed at 4 and 7 months, respectively, after the start of therapy.

Diagnosis of Hurler's syndrome with chest roentgenogram.

Hurler's syndrome is usually diagnosed by chemical means; however, characteristic roentgenographic findings of "hook-shaped" vertebral bodies or "oar-shaped" ribs may be helpful in diagnosing the disorder.