The lectin-like oxidized low density lipoprotein receptor-1 (Lox-1) mediates the recognition and internalization of oxidatively modified low density lipoprotein by vascular endothelial cells. This interaction results in a number of pro-atherogenic cellular responses that probably play a significant role in the pathology of atherosclerosis. The 1.4 Å crystal structure of the extracellular C-type lectin-like domain of human Lox-1 reveals a heart-shaped homodimer with a ridge of six basic amino acids extending diagonally across the apolar top of Lox-1, a central hydrophobic tunnel that extends through the entire molecule, and an electrostatically neutral patch of 12 charged residues that resides next to the tunnel at each opening. Based on the arrangement of critical binding residues on the Lox-1 structure, we propose a binding mode for the recognition of modified low density lipoprotein and other Lox-1 ligands.
Rodent feed is sterilized to eliminate the introduction of potentially pathogenic microorganisms that might result in clinical disease or subclinical infections that could affect physiologic responses. This practice became common as the demand for SPF animals increased. On rare occasions, we have isolated enteric pathogens, including Salmonella spp., Escherichia coli, and Clostridium spp., from unsterilized, natural ingredient rodent feeds (unpublished data). Recent publications regarding the isolation of contemporary, relevant rodent pathogens from rodent diets are unavailable; however, several recent reports implicated the persistence of mouse parvovirus in mouse colonies due to the use of unsterilized feed. 31,40 Current feed sterilization methods are steam autoclaving and irradiation. The chosen method may depend on an institution's capabilities or budget. Steam autoclaves require a large initial capital investment, ongoing maintenance, and a lot of energy to operate. In contrast, few institutions have the capabilities to irradiate feed on a large scale, so most irradiation of feed is performed by or through the feed manufacturers and can add a substantial cost to the feed. Neither method will sterilize all loads 100% of the time. Sterilization depends on load size and ability for adequate quality steam or radiation penetration. Both methods of sterilization can affect the quality of the feed. Many groups, including ours, have shown that autoclaving rodent feed increases feed pellet hardness. 16,35 Feed pellet hardness can affect rodents' ability to eat, especially young animals or strains with dental issues. 23,24 Autoclaving rodent feed can result in decreases in vitamins A, B1, and D; affect protein quality and availability; and alter isoflavone content. 9,15,36 To compensate for the vitamin loss, feed manufacturers often add additional vitamins to the feed mix for autoclavable formulations. Irradiation has little effect on the physical quality of feed but can alter its chemical composition. Feeding an irradiated, purified, AIN76 diet to germ-free mice resulted in high mortality (50%) that was ameliorated with vitamin K supplementation. 20 SPF cats fed an irradiated diet developed a progressive hindlimb ataxia suspected to be due to vitamin A deficiency. 7,13 More recently, irradiation has been shown to increase glycosinolates and the peroxidation of dietary lipids. 8,30 In 2002, studies found that heating foods containing high levels of starches resulted in the production of acrylamide (C 3 H 5 NO; prop-2-enamide) 34 through the Maillard reaction between amino acids (primarily asparagine) and reducing sugars. 26,33,41 Soon after, acrylamide production was demonstrated in autoclaved rodent feed. 37 Acrylamide is a compound used widely in the chemical industry for numerous purposes (paper, grouting agents, water treatment, and cosmetics) and occurs in cigarette smoke. Acrylamide is a neurotoxin, 25 genotoxin, 4,10,12,17
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Escherichia coli pathogenic variants (pathovars) are generally characterized by defined virulence traits and are susceptible to the evolution of hybridized identities due to the considerable plasticity of the E. coli genome. We have isolated a strain from a purified diet intended for research animals that further demonstrates the ability of E. coli to acquire novel genetic elements leading potentially to emergent new pathovars. Utilizing next generation sequencing to obtain a whole genome profile, we report an atypical strain of E. coli, EcoFA807‐17, possessing a tetrathionate reductase (ttr) operon, which enables the utilization of tetrathionate as an electron acceptor, thus facilitating respiration in anaerobic environments such as the mammalian gut. The ttr operon is a potent virulence factor for several enteric pathogens, most prominently Salmonella enterica. However, the presence of chromosomally integrated tetrathionate reductase genes does not appear to have been previously reported in wild‐type E. coli or Shigella. Accordingly, it is possible that the appearance of this virulence factor may signal the evolution of new mechanisms of pathogenicity in E. coli and Shigella and may potentially alter the effectiveness of existing assays using tetrathionate reductase as a unique marker for the detection of Salmonella enterica.
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