Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux.

Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E) lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease

Exercise and Type 2 Diabetes: The American College of Sports Medicine and the American Diabetes Association: joint position statement

Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower type 2 diabetes risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Aerosolized microcystin-LR exacerbates chemokines and other inflammatory mediators of asthma in asthmatic primary human airway epithelium

Microcystin-LR, one of the most abundant and toxic HAB-derived cyanotoxins, has recently been detected in aerosols from HAB water. We previously reported that aerosol MC-LR exposure has a pro-inflammatory influence on the airways. Asthma, which is an extremely prevalent airway disease afflicting approximately 8% of the U.S. population, is largely driven by inflammation. However, the impact of MC-LR aerosol exposure on this at-risk population is unknown. In this study, a 3D primary human airway epithelium model was utilized, in which cells were isolated from healthy and asthmatic donors. An environmentally relevant concentration of MC-LR (1 μM) was aerosolized and delivered to the cell surface, before the cells were harvested for transcriptome analysis. Strikingly, 10% of the genes upregulated (log2FC \u3e 0.25) by asthma alone, were further upregulated by MC-LR exposure including inflammation mediators, such as CXCL11 (log2FC = 0.63); and TLR4 (log2FC = 0.31). These genes had significant associations with pathways, such as “immune cytokine binding” (FDR = 0.015). This study showed that aerosolized MC-LR amplifies the transcriptional differences between asthmatic and healthy donor airway epithelial cells, leading to the exacerbation of inflammatory mediators of asthma, such as chemokines, suggesting a potential for MC-LR exposure to worsen asthma severity