Abeta oligomer toxicity inhibitor protects memory in models of synaptic toxicity

BACKGROUND AND PURPOSE:

Amyloid-ß (Aß) aggregation into synaptotoxic, prefibrillar oligomers is a major pathogenic event underlying the neuropathology of Alzheimer's disease (AD). The pharmacological and neuroprotective properties of a novel Aß aggregation inhibitor, SEN1269, were investigated on aggregation and cell viability and in test systems relevant to synaptic function and memory, using both synthetic Aß(1-42) and cell-derived Aß oligomers.
EXPERIMENTAL APPROACH:

Surface plasmon resonance studies measured binding of SEN1269 to Aß(1-42) . Thioflavin-T fluorescence and MTT assays were used to measure its ability to block Aß(1-42) -induced aggregation and reduction in cell viability. In vitro and in vivo long-term potentiation (LTP) experiments measured the effect of SEN1269 on deficits induced by synthetic Aß(1-42) and cell-derived Aß oligomers. Following i.c.v. administration of the latter, a complex (alternating-lever cyclic ratio) schedule of operant responding measured effects on memory in freely moving rats.
KEY RESULTS:

SEN1269 demonstrated direct binding to monomeric Aß(1-42) , produced a concentration-related blockade of Aß(1-42) aggregation and protected neuronal cell lines exposed to Aß(1-42) . In vitro, SEN1269 alleviated deficits in hippocampal LTP induced by Aß(1-42) and cell-derived Aß oligomers. In vivo, SEN1269 reduced the deficits in LTP and memory induced by i.c.v. administration of cell-derived Aß oligomers.
CONCLUSIONS AND IMPLICATIONS:

SEN1269 protected cells exposed to Aß(1-42) , displayed central activity with respect to reducing Aß-induced neurotoxicity and was neuroprotective in electrophysiological and behavioural models of memory relevant to Aß-induced neurodegeneration. It represents a promising lead for designing inhibitors of Aß-mediated synaptic toxicity as potential neuroprotective agents for treating AD.

Polynomial Model for High-Order and Multi-Carrier Passive Intermodulation Products

Passive intermodulation (PIM) often limits the performance of communication systems, particularly in the presence of multiple carriers. Since the origins of the apparently multiple physical sources of nonlinearity causing PIM in distributed circuits are not fully understood, the behavioural models are frequently employed to describe the process of PIM generation. In this paper, a memoryless nonlinear polynomial model, capable of predicting high-order multi-carrier intermodulation products, is deduced from the third-order two-tone PIM measurements on a microstrip transmission line with distributed nonlinearity. The analytical model of passive distributed nonlinearity is implemented in Keysight Technology’s ADS simulator to evaluate the adjacent band power ratio for three-tone signals. The obtained results suggest that the costly multi-carrier test setups can possibly be replaced by a simulation tool based on the properly retrieved nonlinear polynomial model.

Behavioural context of multi-scale species distribution models assessed by radio-tracking

Incorporating ecological processes and animal behaviour into Species Distribution Models (SDMs) is difficult. In species with a central resting or breeding place, there can be conflict between the environmental requirements of the 'central place' and foraging habitat. We apply a multi-scale SDM to examine habitat trade-offs between the central place, roost sites, and foraging habitat in . Myotis nattereri. We validate these derived associations using habitat selection from behavioural observations of radio-tracked bats. A Generalised Linear Model (GLM) of roost occurrence using land cover variables with mixed spatial scales indicated roost occurrence was positively associated with woodland on a fine scale and pasture on a broad scale. Habitat selection of radio-tracked bats mirrored the SDM with bats selecting for woodland in the immediate vicinity of individual roosts but avoiding this habitat in foraging areas, whilst pasture was significantly positively selected for in foraging areas. Using habitat selection derived from radio-tracking enables a multi-scale SDM to be interpreted in a behavioural context. We suggest that the multi-scale SDM of . M. nattereri describes a trade-off between the central place and foraging habitat. Multi-scale methods provide a greater understanding of the ecological processes which determine where species occur and allow integration of behavioural processes into SDMs. The findings have implications when assessing the resource use of a species at a single point in time. Doing so could lead to misinterpretation of habitat requirements as these can change within a short time period depending on specific behaviour, particularly if detectability changes depending on behaviour. © 2011 Gesellschaft für ökologie.

How Do Trainees Rate the Impact of a Short Cognitive Behavioural Training Programme on their Knowledge and Skills?

Background: A strong evidence base for cognitive behavioural therapy has led to CBT models becoming available within mainstream mental health services. As the concept of stepped care develops, new less intensive mental health interventions such as guided self-help are emerging, delivered by staff not trained to the level of accredited Cognitive Behavioural Therapists. Aim: The aim of this study was to determine how mental health staff evaluated the usefulness of a short training programme in CBT concepts, models and techniques for routine clinical practice.
Method: A cohort of mental health staff (n = 102) completed pre- and posttraining self-report questionnaires measuring trainee perceptions of the impact of a short training programme on knowledge and skills. Mentors and managers were also asked to comment on perceived impact of the training.
Results: Trainees and mentors reported perceived gains in knowledge and skills posttraining and at 1-year follow-up. Managers and trainees reported perceived improvements in skills and practice. Conclusion: A short Cognitive Behavioural skills programme can enable mental health staff to integrate basic CB knowledge and skills into routine clinical practice.

Τesting models for the beginnings of the Aurignacian and the advent of figurative art and music: The radiocarbon chronology of Geißenklösterle

The German site of Geißenklösterle is crucial to debates concerning the European Middle to Upper Palaeolithic transition and the origins of the Aurignacian in Europe. Previous dates from the site are
central to an important hypothesis, the Kulturpumpe model, which posits that the Swabian Jura was an area where crucial behavioural developments took place and then spread to other parts of Europe. The previous chronology (critical to the model), is based mainly on radiocarbon dating, but remains poorly constrained due to the dating resolution and the variability of dates. The cause of these problems is disputed, but two principal explanations have been proposed: a) larger than expected variations in the production of atmospheric radiocarbon, and b) taphonomic in?uences in the site mixing the bones that were dated into different parts of the site. We reinvestigate the chronology using a new series of radiocarbon determinations obtained from the Mousterian, Aurignacian and Gravettian levels. The results strongly imply that the previous dates were affected by insuf?cient decontamination of the bone collagen prior to dating. Using an ultra?ltration protocol the chronometric picture becomes much clearer. Comparison of the results against other recently dated sites in other parts of Europe suggests the Early Aurignacian levels are earlier than other sites in the south of France and Italy, but not as early as recently dated sites which suggest a pre-Aurignacian dispersal of modern humans to Italy byw45000 cal BP. They are consistent with the importance of the Danube Corridor as a key route for the movement of people and ideas. The new dates fail to refute the Kulturpumpe model and suggest that Swabian Jura is a region that contributed signi?cantly to the evolution of symbolic behaviour as indicated by early evidence for ?gurative art, music and mythical imagery. © 2012 Elsevier Ltd. All rights reserved.