p73 Regulates Neurodegeneration and Phospho-Tau Accumulation during Aging and Alzheimer's Disease

SummaryThe genetic mechanisms that regulate neurodegeneration are only poorly understood. We show that the loss of one allele of the p53 family member, p73, makes mice susceptible to neurodegeneration as a consequence of aging or Alzheimer's disease (AD). Behavioral analyses demonstrated that old, but not young, p73+/− mice displayed reduced motor and cognitive function, CNS atrophy, and neuronal degeneration. Unexpectedly, brains of aged p73+/− mice demonstrated dramatic accumulations of phospho-tau (P-tau)-positive filaments. Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. The increase in P-tau was likely mediated by JNK; in p73+/− neurons, the activity of the p73 target JNK was enhanced, and JNK regulated P-tau levels. Thus, p73 is essential for preventing neurodegeneration, and haploinsufficiency for p73 may be a susceptibility factor for AD and other neurodegenerative disorders

Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic

MRI-detectable changes in mouse brain structure induced by voluntary exercise

Physical exercise, besides improving cognitive and mental health, is known to cause structural changes in the brain. Understanding the structural changes that occur with exercise as well as the neuroanatomical correlates of a predisposition for exercise is important for understanding human health. This study used high-resolution 3D MR imaging, in combination with deformation-based morphometry, to investigate the macroscopic changes in brain structure that occur in healthy adult mice following four weeks of voluntary exercise. We found that exercise induced changes in multiple brain structures that are involved in motor function and learning and memory including the hippocampus, dentate gyrus, stratum granulosum of the dentate gyrus, cingulate cortex, olivary complex, inferior cerebellar peduncle and regions of the cerebellum. In addition, a number of brain structures, including the hippocampus, striatum and pons, when measured on MRI prior to the start of exercise were highly predictive of subsequent exercise activity. Exercise tended to normalize these pre-existing differences between mice.This work was funded by Canadian Institutes of Health Research Grant MOP231389 and the Ontario Preclinical Imaging Consortium from the Ontario Research Fund

Mapping canopy traits over Québec using airborne and spaceborne imaging spectroscopy

Abstract The advent of new spaceborne imaging spectrometers offers new opportunities for ecologists to map vegetation traits at global scales. However, to date most imaging spectroscopy studies exploiting satellite spectrometers have been constrained to the landscape scale. In this paper we present a new method to map vegetation traits at the landscape scale and upscale trait maps to the continental level, using historical spaceborne imaging spectroscopy (Hyperion) to derive estimates of leaf mass per area, nitrogen, and carbon concentrations of forests in Québec, Canada. We compare estimates for each species with reference field values and obtain good agreement both at the landscape and continental scales, with patterns consistent with the leaf economic spectrum. By exploiting the Hyperion satellite archive to map these traits and successfully upscale the estimates to the continental scale, we demonstrate the great potential of recent and upcoming spaceborne spectrometers to benefit plant biodiversity monitoring and conservation efforts