Cross-Sectional Comparison of Small Animal [18F]-Florbetaben Amyloid-PET between Transgenic AD Mouse Models

We aimed to compare [¹⁸F]-florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer’s disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p<0.05) at eight months (N = 7) to 1.07±0.04 (p<0.005) at ten months (N = 6), 1.28±0.06 (p<0.001) at 16 months (N = 6) and 1.39±0.09 (p<0.001) at 19 months (N = 6). SUVR was 0.95±0.03 in WT mice of all ages (N = 22). In APPswe/PS1G384A mice, the SUVR was 0.93/0.98 at five months (N = 2) and 1.11 at 16 months (N = 1). In APPswe/PS1dE9 mice, the SUVR declined from 0.96/0.96 at 12 months (N = 2) to 0.91/0.92 at 24 months (N = 2), due to β-amyloid plaques in cerebellum. PVEC reduced the discrepancy between SUVR-PET and autoradiography from −22% to +2% and increased the differences between young and aged transgenic animals. SUVR and plaque load correlated highly between strains for uncorrected (R = 0.94, p<0.001) and PVE-corrected (R = 0.95, p<0.001) data. We find that APPswe/PS2 mice may be optimal for longitudinal amyloid-PET monitoring in planned interventions studies.     

Spatial and temporal variation in harvest probabilities for American black duck

Assessing spatial variation in waterfowl harvest probabilities from banding data is challenging because reporting and recovery probabilities have distinct spatial patterns that covary temporally with harvesting regulations, hunter effort, and reporting methods. We analyzed direct band recovery data from American black ducks banded on the Canadian breeding grounds from 1970 through 2010. Data were registered to a 1‐degree grid and analyzed using hierarchical logistic regression models with spatially correlated errors to estimate the annual probabilities of band recovery and the proportion of individuals recovered in Canada. Probability of harvest was estimated from these values, in combination with independent estimates of reporting probabilities in Canada and the USA. Model covariates included estimates of hunting effort and factors for harvest regulation and band reporting methods. Both the band recovery processes and the proportion of individuals recovered in Canada had significant spatial structure. Recovery probabilities were highest in southern Ontario, along the Saint Lawrence River in Quebec, and in Nova Scotia. Black ducks breeding in Nova Scotia and southern Quebec were harvested predominantly in Canada. Recovery probabilities for juveniles were correlated with hunter effort, while the adult recoveries were weakly correlated with the implementation of stricter harvest regulations in the early 1980s. Mean harvest probability decreased in the northern portion of the survey area but remained stable or even increased in the south. Harvest probabilities for juveniles in 2010 exceeded 20% in southern Quebec and the Atlantic provinces. Our results demonstrate fine‐scale variation in harvest probabilities for black duck on the Canadian breeding ground. In particular, harvest probabilities should be closely monitored along the Saint Lawrence River system and in the Atlantic provinces to avoid overexploitation.     

2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors

Starting from previously disclosed equally potent cathepsin K and S inhibitor 4-propyl-6-(3-trifluoromethylphenyl)pyrimidine-2-carbonitrile 1, a novel 2-phenyl-9H-purine-6-carbonitrile scaffold was identified to provide potent and selective cathepsin S inhibitors.     

Piperazine sulfonamide BACE1 inhibitors: Design,synthesis, and in vivo characterization

With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ₄₀ in transgenic mice with a single subcutaneous dose.     

6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as cathepsin S inhibitors

6-Phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile analogues were identified as potent and selective cathepsin S inhibitor against both purified enzyme and in human JY cell based cellular assays. This core has a very stable thio-trapping nitrile war-head in comparison with the well reported pyrimidine-2-carbonitrile cysteine cathepsin inhibitors. Compound 47 is also very potent in in vivo mouse spleenic Lip10 accumulation assays.     

A novel series of positive modulators of the AMPA receptor: Structure-based lead optimization

Starting from lead compound 1, we demonstrate how X-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity.     

Error bars in experimental biology

Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what error bars represent. We suggest eight simple rules to assist with effective use and interpretation of error bars.     

Size matters: variations in seagrass seed size at local scales affects seed performance

Hydrobiologia - Seed size can have an impact on angiosperm reproductive fitness. Ecological theory predicts plants that will produce larger seeds in stressful environments to increase the chances...     

Spatiotemporal and teratological analyses of diatom assemblages from sediments contaminated with industrial effluents in the St. Lawrence River near Cornwall (Ontario,Canada)

Hydrobiologia - Throughout the twentieth century, waterfront industries in Cornwall (Ontario, Canada) discharged significant quantities of mercury (Hg) and other industrial effluents to the St....     

Genetic portrait of Lisboa immigrant population from Cabo Verde with mitochondrial DNA analysis

Journal of Genetics -