Bile induces pleiotropic responses that affect production of virulence factors, motility, and other phenotypes in the enteric pathogen Vibrio cholerae. Since bile is a heterogeneous mixture, crude bile was fractionated, and the components that mediate virulence gene repression and enhancement of motility were identified by nuclear magnetic resonance, gas chromatography (GC), and GC-mass spectrometry analyses. The unsaturated fatty acids detected in bile, arachidonic, linoleic, and oleic acids, drastically repressed expression of the ctxAB and tcpA genes, which encode cholera toxin and the major subunit of the toxin-coregulated pilus, respectively. The unsaturated fatty acid-dependent repression was due to silencing of ctxAB and tcpA expression by the histonelike nucleoid-structuring protein H-NS, even in the presence of the transcriptional activator ToxT. Unsaturated fatty acids also enhanced motility of V. cholerae due to increased expression of flrA, the first gene of a regulatory cascade that controls motility. H-NS had no role in the fatty acid-mediated enhancement of motility. It is likely that the ToxR/ToxT system that negatively regulates motility is rendered nonfunctional in the presence of unsaturated fatty acids, leading to an increase in motility. Motility and flrA expression were also increased in the presence of cholesterol, another component of bile, in an H-NS-and ToxR/ToxT-independent manner.Vibrio cholerae, a noninvasive enteric bacterium, is the causative agent of the diarrheal disease cholera. Cholera continues to cause devastating outbreaks, particularly in the developing world, resulting in more than 100,000 deaths every year, and the case fatality ratio may exceed 20% in affected populations (29). The pathogenicity of V. cholerae is largely due to the production of cholera toxin (CT) and a toxin-coregulated pilus (TCP), thought to be essential for colonization of the intestinal epithelium by the bacterium (13). Expression of CT, TCP, and several other virulence factors is coordinately controlled by the hierarchical expression of regulatory proteins comprising the ToxR regulon (14), in which the inner membrane DNA binding proteins ToxR and TcpP (7, 18) activate expression of ToxT, a transcriptional regulator that is required for the expression of ctxAB and tcpA as well as several other virulence genes (3). The ToxR regulon is strongly influenced by physicochemical parameters/factors such as temperature, osmolarity, pH, amino acids, and bile, which exert their effects at different levels of the regulatory cascade (16, 25).Bile, a heterogeneous mixture of conjugated and unconjugated bile acids, bile pigments, inorganic salts, cholesterol, phospholipids, and probably other unidentified components, is secreted into the lumen of the duodenum from the gall bladder through the bile duct and is inevitably encountered by all enteric bacteria in their human hosts (9). The role of bile in normal gastrointestinal physiology is to aid the emulsification of lipids and also to protect the host from bacteri...

More people globally depend on the water buffalo than any other domesticated species, and as the most closely related domesticated species to cattle they can provide important insights into the shared evolutionary basis of domestication. Here, we sequence the genomes of 79 water buffalo across seven breeds and compare patterns of between breed selective sweeps with those seen for 294 cattle genomes representing 13 global breeds. The genomic regions under selection between cattle breeds significantly overlap regions linked to stature in human genetic studies, with a disproportionate number of these loci also shown to be under selection between water buffalo breeds. Investigation of potential functional variants in the water buffalo genome identifies a rare example of convergent domestication down to the same mutation having independently occurred and been selected for across domesticated species. Cross-species comparisons of recent selective sweeps can consequently help identify and refine important loci linked to domestication.

PNH is an uncommon disease in children and should be included in the differential diagnosis of children presenting with cytopenia.