Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

Genome-wide microarray analysis (Affymetrix array) was used (i) to determine whether only one gene, the cytochrome P450 enzyme Cyp6g1, is differentially transcribed in dichlorodiphenyltrichloroethane (DDT)-resistant vs. -susceptible Drosophila; and (ii) to profile common genes differentially transcribed across a DDT-resistant field isolate [Rst(2)DDT Wisconsin ] and a laboratory DDT-selected population [Rst(2)DDT 91-R ]. Statistical analysis (ANOVA model) identified 158 probe sets that were differentially transcribed among Rst(2)DDT 91-R , Rst(2)DDT Wisconsin , and the DDT-susceptible genotype Canton-S (P < 0.01). The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene (Dbi) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila, and this difference was significant at the most stringent statistical level, a Bonferroni correction. The list of potential candidates differentially transcribed also includes 63 probe sets for which molecular function ontology annotation of the probe sets did not exist. A total of four genes (Cyp6a2, Dbi, Uhg1, and CG11176) were significantly different (P < 5.6 e ؊06 ) between Rst(2)DDT 91-R and Canton-S. Additionally, two probe sets encoding Cyp12d1 and Dbi were significantly different between Rst(2)DDT Wisconsin and Canton-S after a Bonferroni correction. Fifty-two probe sets, including those associated with pesticide detoxification, ion transport, signal transduction, RNA transcription, and lipid metabolism, were commonly expressed in both resistant lines but were differentially transcribed in Canton-S. Our results suggest that more than Cyp6g1 is overtranscribed in field and laboratory DDT-resistant genotypes, and the number of commonalities suggests that similar resistance mechanisms may exist between laboratory-and field-selected DDT-resistant fly lines.T he evolution of insecticide resistance is often, but not always, based on major effect alleles (1-4). It has been hypothesized that high selection pressure in the field will favor monogenic forms of pesticide resistance, and that selection for resistance in the laboratory will favor polygenic resistance (5-7). In early genetic studies in Drosophila, dichlorodiphenyltrichloroethane (DDT) resistance was mapped to multiple locations on chromosomes II and III (8-14). Subsequently, low-level DDT resistance was mapped to 64.5 Ϯ 2 centiMorgans on the second chromosome (15), a locus (loci) known as Rst(2)DDT.Recently, Daborn et al. (16) suggested that resistance to DDT in the field is monogenic and is due to the overexpression of a single P450 gene, Cyp6g1. Le Goff et al. (17) suggested that resistance in field isolates of both Drosophila melanogaster and Drosophila simulans is associated with overtranscription of Cyp6g1, whereas prolonged laboratory selection with DDT apparently coselects additional genes such as Cyp12d1 (18) To date, no genome-wide expression profile has been evaluated to investigate the extent to which gene transcription varies between genotypes that are resis...

Background The molecular basis for the focal nature of atherosclerotic lesions is poorly understood. Here, we explored whether disturbed flow patterns activate an innate immune response to form the NLRP3 inflammasome scaffold in vascular endothelial cells (ECs) via sterol regulatory element binding protein 2 (SREBP2). Methods and Results Oscillatory flow activates SREBP2 and induces NLRP3 inflammasome in ECs. The underlying mechanisms involve SREBP2 transactivating NADPH oxidase 2 (NOX2) and NLRP3. Consistently, SREBP2, NOX2, and NLRP3 levels were elevated in atheroprone areas of mouse aortas, suggesting that the SREBP2-activated NLRP3 inflammasome causes functionally disturbed endothelium with increased inflammation. Mimicking the effect of atheroprone flow, EC-specific overexpression of the activated form of SREBP2 synergized with hyperlipidemia to increase atherosclerosis in the atheroresistant areas of mouse aortas. Conclusions Atheroprone flow induces NLRP3 inflammasome in endothelium through SREBP2 activation. This increased innate immunity in endothelium synergizes with hyperlipidemia to cause topographic distribution of atherosclerotic lesions.