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Bacterial type III secretion systems (T3SSs) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of pathogenic E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that 22 of 26 sequence type (ST) 69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. Analysis of published E. coli genomes with worldwide representation showed that ST69 contained an intact ETT2 in these strains as well. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has importance in infection, although its exact functional role remains obscure.Infection with multiple drug resistant (MDR) Escherichia coli poses a life threat to immunocompromised pediatric cancer patients. Our aim is to genotypically characterize the plasmids harbored in MDR E. coli isolates recovered from bacteremic patients of Children's Cancer Hospital in Egypt 57357 (CCHE 57357). In this study, 21 carbapenem-resistant E. coli (CRE) isolates were selected that exhibit Quinolones and Aminoglycosides resistance. Plasmid shot-gun sequencing was performed using Illumina next- generation sequencing platform. Isolates demonstrated resistant to all beta-lactams, carbapenems, aminoglycosides and quinolones. Of the 32 antimicrobial resistant genes identified that exceeded the analysis cutoff coverage, the highest represented genes were aph(6)-Id, sul2, aph(3″)-Ib, aph(3')-Ia, sul1, dfrA12, TEM-220, NDM-11. Isolates employed a wide array of resistance mechanisms including antibiotic efflux, antibiotic inactivation, antibiotic target replacements and antibiotic target alteration. Sequenced isolates displayed diverse insertion sequences, including IS26, suggesting dynamic reshuffling of the harbored plasmids. Most isolates carried plasmids originating from other bacterial species suggesting a possible horizontal gene transfer. Only two isolates showed virulence factors with iroA gene cluster which was found in only one of them. Outside the realms of nosocomial infections among patients in hospitals, our results indicate a transfer of resistant genes and plasmids across different organisms.Early 2 factor (E2F) family transcription factors participate in myriad cell biological processes including the cell cycle, DNA repair, apoptosis, development, differentiation, and metabolism. Circadian rhythms influence many of these phenomena. Here we find that a mammalian circadian rhythm component, Cryptochrome 2 (CRY2), regulates E2F family members. Furthermore, CRY1 and CRY2 cooperate with the E3 ligase complex SKP-CULLIN-FBXL3 (SCFFBXL3) to reduce E2F steady state protein levels. These findings reveal an unrecognized molecular connection between circadian clocks and cell cycle regulation and highlight another mechanism to maintain appropriate E2F protein levels for proper cell growth.Combination use of digoxin and other medications might lead to worse outcomes in patients with atrial fibrillation (AF). We sought to investigate whether digoxin-amiodarone combination would lead to worse outcome than digoxin alone in patients with AF. Adult patients with AF and received digoxin treatment from random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included. Baseline characteristics including risk factors and medications were matched by propensity score (PS) in those with and without addition of amiodarone treatment. A total of 5,040 AF patients taking digoxin therapy was included. PS matching identified 1,473 patients receiving digoxin-amiodarone combination and 2,660 patients receiving digoxin with a median follow-up of 1,331 days. Digoxin-amiodarone combination was associated with increased all-cause mortality (adjusted hazard ratio (HR) 1.640, 95% confidence interval (CI) 1.470-1.829, P  less then  0.001). The risk of mortality increased regardless of duration of combination. Risk of sudden cardiac death was not increased in the combination group (HR 1.304, 95% CI 1.049-1.622, P = 0.017). Death due to non-arrhythmic cardiac disease, cerebrovascular disease, and other vascular disease were higher in the combination group than the digoxin group. In conclusion, in patients with AF, digoxin-amiodarone combination therapy is associated with excess mortality than digoxin alone.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Environmental radioactive contamination caused by the Fukushima Dai-ichi Nuclear Power Plant accident has aroused great concern regarding a possible increase in the incidence of childhood thyroid cancer. The ultrasound examinations were conducted immediately after the accident as part of the Fukushima Health Management Survey (FHMS), which is divided into the preliminary baseline survey (PBLS) and the full-scale survey (FSS). Some of their outcomes are reported regularly and made available to the public. AZD3965 We have detailed measurements of the air-dose rates and radioactive elements in soil in many places all over the Fukushima prefecture. To study the dose-response relationship, we begin with the assumption that the external and internal doses are correlated with the air-dose rate and the amount of 131I in soil, respectively. We then investigate the relationship between these estimated doses and the PBLS and FSS thyroid cancer cases. Our analysis shows that the dose-response curve with the FSS data clearly differs from that with the PBLS data.