Endothelial Dysfunction in the Apolipoprotein E-deficient Mouse: insights into the influence of diet, gender and aging

Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements that have contributed to elucidating the mechanisms pertaining to vascular dysfunction in the apoE-/- mouse. First, we summarize lipoproteins and atherosclerosis phenotypes in the apoE-/- mouse, and then we briefly discuss controversial evidence relative to the influence of gender on the development of atherosclerosis in this murine model. Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE-/- mouse

Cardiac and vascular phenotypes in the apolipoprotein E-deficient mouse

Cardiovascular death is frequently associated with atherosclerosis, a chronic multifactorial disease and a leading cause of death worldwide. Genetically engineered mouse models have proven useful for the study of the mechanisms underlying cardiovascular diseases. The apolipoprotein E-deficient mouse has been the most widely used animal model of atherosclerosis because it rapidly develops severe hypercholesterolemia and spontaneous atherosclerotic lesions similar to those observed in humans. In this review, we provide an overview of the cardiac and vascular phenotypes and discuss the interplay among nitric oxide, reactive oxygen species, aging and diet in the impairment of cardiovascular function in this mouse model

Quantum transport in ultracold atoms

Ultracold atoms confined by engineered magnetic or optical potentials are ideal systems for studying phenomena otherwise difficult to realize or probe in the solid state because their atomic interaction strength, number of species, density, and geometry can be independently controlled. This review focuses on quantum transport phenomena in atomic gases that mirror and oftentimes either better elucidate or show fundamental differences with those observed in mesoscopic and nanoscopic systems. We discuss significant progress in performing transport experiments in atomic gases, contrast similarities and differences between transport in cold atoms and in condensed matter systems, and survey inspiring theoretical predictions that are difficult to verify in conventional setups. These results further demonstrate the versatility offered by atomic systems in the study of nonequilibrium phenomena and their promise for novel applications.Comment: 24 pages, 7 figures. A revie

Fano Resonances in Flat Band Networks

Linear wave equations on Hamiltonian lattices with translational invariance are characterized by an eigenvalue band structure in reciprocal space. Flat band lattices have at least one of the bands completely dispersionless. Such bands are coined flat bands. Flat bands occur in fine-tuned networks, and can be protected by (e.g. chiral) symmetries. Recently a number of such systems were realized in structured optical systems, exciton-polariton condensates, and ultracold atomic gases. Flat band networks support compact localized modes. Local defects couple these compact modes to dispersive states and generate Fano resonances in the wave propagation. Disorder (i.e. a finite density of defects) leads to a dense set of Fano defects, and to novel scaling laws in the localization length of disordered dispersive states. Nonlinearities can preserve the compactness of flat band modes, along with renormalizing (tuning) their frequencies. These strictly compact nonlinear excitations induce tunable Fano resonances in the wave propagation of a nonlinear flat band lattice

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons