Analysis of alteration of p75NTR processing and signalling by PS2 mutation and gamma-secretase inhibition

The presenilins (PSs) were identified as causative genes in cases of early-onset familial Alzheimer's disease (AD) and current evidence indicates that PSs are part of the gamma-secretase complex responsible for proteolytic processing of type I membrane proteins. p75NTR, a common neurotrophin receptor, was shown to be subject to gamma-secretase processing. However, it is not clear if the p75NTR downstream signal is altered in response to gamma-secretase cleavage, and further there is a possibility that AD-related PS mutations may affect this cleavage, resulting in pathogenic alterations in signal transduction. In this study, we confirmed that p75NTR downstream signalling is altered by PS2 mutation or gamma-secretase inhibition in SHSY-5Y cells. The activity of the small GTPase RhoA is strongly affected by these treatments. This study demonstrates that gamma-secretase and PS2 play an important role in regulating neurotrophin signal transduction and either mutation of PS2 or inhibition of gamma-secretase disturbs this function.

Processing, Annealing and Sterilisation of Poly-L-Lactide.

Poly--lactide (PLLA) is one of the most significant members of a group of polymers regarded as bioabsorbable. Degradation of PLLA proceeds through hydrolysis of the ester bonds in the polymer chains and is influenced significantly by the polymer's molecular weight and crystallinity. To evaluate the effects of processing and sterilisation on these properties, PLLA pellets were either compression moulded or extruded, subjected to annealing at 120°C for 4 h and sterilised by ethylene oxide (EtO) gas. Procedures were used to evaluate the mechanical properties, molecular weight and crystallinity. Upon processing, the crystallinity of the material fell from 61% for the PLLA pellets to 12% and 20% for the compressed and extruded components, respectively. After annealing, crystallinity increased to 43% for the compression-moulded material and 40% for the extruded material. Crystallinity further increased upon EtO sterilisation. A slight decrease in molecular weight was observed for the extruded material through processing, annealing and sterilisation. Young's modulus generally increased with increasing crystallinity, and extension at break and tensile strength decreased. The results from this investigation suggest that PLLA is sensitive to processing and sterilisation, altering properties critical to its degradation rate.

Processing characteristics and mechanical properties of metallocene catalyzed linear low-density polyethylene foams for rotational molding

The object of this work is to assess the suitability of metallocene catalyzed linear low-density polyethylenes for the rotational molding of foams and to link the material and processing conditions to cell morphology and part mechanical properties (flexural and compressive strength). Through adjustments to molding conditions, the significant processing and physical material parameters that optimize metallocene catalyzed linear low-density polyethylene foam structure have been identified. The results obtained from an equivalent conventional grade of Ziegler-Natta catalyzed linear low-density polyethylene are used as a basis for comparison. The key findings of this study are that metallocene catalyzed LLDPE can be used in rotational foam molding to produce a foam that will perform as well as a ZieglerNatta catalyzed foam and that foam density Is by far the most Influential factor over mechanical properties of foam. © 2004 Society of Plastics Engineers.