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.

Breast Cancer Risk in Relation to Occupations with Exposure to Carcinogens and Endocrine Disruptors:a Canadian Case-Control Study

Background

Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours.

Methods

1005 breast cancer cases referred by a regional cancer center and 1147 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case?control design, exposure effects were estimated using conditional logistic regression.

Results

Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5).

Conclusions

These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work histories in environmental and occupational epidemiology.

A Tunable Encryption Scheme and Analysis of Fast Selective Encryption for CAVLC and CABAC in H.264/AVC

Recently, two fast selective encryption methods for context-adaptive variable length coding and context-adaptive binary arithmetic coding in H.264/AVC were proposed by Shahid et al. In this paper, it was demonstrated that these two methods are not as efficient as only encrypting the sign bits of nonzero coefficients. Experimental results showed that without encrypting the sign bits of nonzero coefficients, these two methods can not provide a perceptual scrambling effect. If a much stronger scrambling effect is required, intra prediction modes, and the sign bits of motion vectors can be encrypted together with the sign bits of nonzero coefficients. For practical applications, the required encryption scheme should be customized according to a user's specified requirement on the perceptual scrambling effect and the computational cost. Thus, a tunable encryption scheme combining these three methods is proposed for H.264/AVC. To simplify its implementation and reduce the computational cost, a simple control mechanism is proposed to adjust the control factors. Experimental results show that this scheme can provide different scrambling levels by adjusting three control factors with no or very little impact on the compression performance. The proposed scheme can run in real-time and its computational cost is minimal. The security of the proposed scheme is also discussed. It is secure against the replacement attack when all three control factors are set to one.

Between-taxon matching of common and rare species richness patterns

Aim: Our primary aim is to understand how assemblages of rare (restricted range) and common (widespread) species are correlated with each other among different taxa. We tested the proposition that marine species richness patterns of rare and common species differ, both within a taxon in their contribution to the richness pattern of the full assemblage and among taxa in the strength of their correlations with each other. Location The UK intertidal zone. Methods: We used high-resolution marine datasets for UK intertidal macroalgae, molluscs and crustaceans each with more than 400 species. We estimated the relative contribution of rare and common species, treating rarity and commonness as a continuous spectrum, to spatial patterns in richness using spatial crosscorrelations. Correlation strength and significance was estimated both within and between taxa. Results: Common species drove richness patterns within taxa, but rare species contributed more when species were placed on an equal footing via scaling by binomial variance. Between taxa, relatively small sub-assemblages (fewer than 60 species) of common species produced the maximum correlation with each other, regardless of taxon pairing. Cross-correlations between rare species were generally weak, with maximum correlation occurring between small sub-assemblages in only one case. Cross-correlations between common and rare species of different taxa were consistently weak or absent. Main conclusions: Common species in the three marine assemblages were congruent in their richness patterns, but rare species were generally not. The contrast between the stronger correlations among common species and the weak or absent correlations among rare species indicates a decoupling of the processes driving common and rare species richness patterns. The internal structure of richness patterns of these marine taxa is similar to that observed for terrestrial taxa.