The Guinea Pig as a model for sporadic Alzheimer's Disease (AD): the impact of cholesterol intake on expression of AD-related genes

Extent: 12p.We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes.Mathew J. Sharman, Seyyed H. Moussavi Nik, Mengqi M. Chen, Daniel Ong, Linda Wijaya, Simon M. Laws, Kevin Taddei, Morgan Newman, Michael Lardelli, Ralph N. Martins, Giuseppe Verdil

Racial, Ethnic and Gender Inequities in Farmland Ownership and Farming in the US

This paper provides an analysis of U.S. farmland owners, operators, and workers by race, ethnicity, and gender. We first review the intersection between racialized and gendered capitalism and farmland ownership and farming in the United States. Then we analyze data from the 2014 Tenure and Ownership Agricultural Land survey, the 2012 Census of Agriculture, and the 2013–2014 National Agricultural Worker Survey to demonstrate that significant nation-wide disparities in farming by race, ethnicity and gender persist in the U.S. In 2012–2014, White people owned 98% and operated 94% of all farmland. They generated 98% of all farm-related income from land ownership and 97% of income from farm owner-operatorship. Meanwhile, People of Color farmers (African American or Black, Asian American, Native American, Hawaiian or other Pacific Islander, and Hispanic farmers) were more likely to be tenants rather than owners, owned less land, and generated less farm-related wealth per person than their White counterparts. Hispanic farmers were also disproportionately farm laborers. In addition to racial and ethnic disparities, there were disparities by gender. About 63% of non-operating landowners, 86% of farm operators, and 87% of tenant farmers were male, and female farmers tended to generate less income per farmer than men. This data provides evidence of ongoing racial, ethnic and gender disparities in agriculture in the United States. We conclude with a call to address the structural drivers of the disparities and with recommendations for better data collection