Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age

Background

Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of Aβ peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for their cognate disorders. Detection of the aggregated species requires sensitive tools that efficiently discriminate them from monomers of the same proteins. Here we have established a proximity ligation assay (PLA) for specific and sensitive detection of Aβ protofibrils via simultaneous recognition of three identical determinants present in the aggregates. PLA is a versatile technology in which the requirement for multiple target recognitions is combined with the ability to translate signals from detected target molecules to amplifiable DNA strands, providing very high specificity and sensitivity.

Results

For specific detection of Aβ protofibrils we have used a monoclonal antibody, mAb158, selective for Aβ protofibrils in a modified PLA, where the same monoclonal antibody was used for the three classes of affinity reagents required in the assay. These reagents were used for detection of soluble Aβ aggregates in solid-phase reactions, allowing detection of just 0.1 pg/ml Aβ protofibrils, and with a dynamic range greater than six orders of magnitude. Compared to a sandwich ELISA setup of the same antibody the PLA increases the sensitivity of the Aβ protofibril detection by up to 25-fold. The assay was used to measure soluble Aβ aggregates in brain homogenates from mice transgenic for a human allele predisposing to Aβ aggregation.

Conclusions

The proximity ligation assay is a versatile analytical technology for proteins, which can provide highly sensitive and specific detection of Aβ aggregates - and by implication other protein aggregates of relevance in Alzheimer's disease and other neurodegenerative disorders.     

Comparison of Fractionation Methods for the Characterisation of Short Chain Branching as a Function of Molecular Weight in Ethylene 1-Olefin Copolymers

Summary: Rapid and automated analysis of polyolefins is becoming essential for product development in industry. Quantifying short chain branching in ethylene 1-olefin copolymers is common practice. Several different methods are available to perform this type of analysis. Preparative fractionation followed by subsequent analysis of the fraction by SEC and NMR, SEC-FTIR and SEC-IR were studied towards their applicability in polyolefin research and product development environment. The method of choice is defined by prerequisites such as accuracy, labour and time demands but also in versatility and practicability. The most accurate method is limited in terms of sample throughput and the most practical method is limited towards resolution of very low branching. SEC-FTIR is capable to measure even heterogeneous low branched samples like bimodal high density polyethylene in rapid and satisfactory matter.     

An efficient synthesis of pregaliellalactone and desoxygaliellalactone

A short and efficient total synthesis of rac-desoxygaliellalactone and (+)-desoxygaliellalactone, via the biosynthetic intermediate pregaliellalactone, is described. The synthesis was achieved in only three steps, for (+)-desoxygaliellalactone including an enantioselective alkyl propiolate addition to 4-pentenal, a palladium catalysed alkylative lactonisation and an intramolecular Diels–Alder cycloaddition.