Glycolytic and Gluconeogenic Growth of \u3cem\u3eEscherichia coli\u3c/em\u3e O157:H7 (EDL933) and \u3cem\u3eE. coli\u3c/em\u3e K-12 (MG1655) in the Mouse Intestine

Escherichia coli EDL933, an O157:H7 strain, is known to colonize the streptomycin-treated CD-1 mouse intestine by growing in intestinal mucus (E. A. Wadolkowski, J. A. Burris, and A. D. O\u27Brien, Infect. Immun. 58:2438-2445, 1990), but what nutrients and metabolic pathways are employed during colonization has not been determined. In this study, when the wild-type EDL933 strain was fed to mice along with an EDL933 ΔppsA ΔpckA mutant, which is unable to utilize tricarboxylic acid cycle intermediates and gluconeogenic substrates for growth, both strains colonized the mouse intestine equally well. Therefore, EDL933 utilizes a glycolytic substrate(s) for both initial growth and maintenance when it is the only E. coli strain fed to the mice. However, in the presence of large numbers of MG1655, a K-12 strain, it is shown that EDL933 utilizes a glycolytic substrate(s) for initial growth in the mouse intestine but appears to utilize both glycolytic and gluconeogenic substrates in an attempt to maintain colonization. It is further shown that MG1655 predominantly utilizes glycolytic substrates for growth in the mouse intestine whether growing in the presence or absence of large numbers of EDL933. Data are presented showing that although small numbers of EDL933 grow to large numbers in the intestine in the presence of large numbers of MG1655 when both strains are fed to mice simultaneously, precolonization with MG1655 affords protection against subsequent colonization by EDL933. Moreover, in mice that are precolonized with EDL933, small numbers of MG1655 are able to grow rapidly in the intestine and EDL933 is eliminated. In situ hybridization experiments using E. coli-specific rRNA probes showed that while MG1655 is found only in mucus, EDL933 is found both in mucus and closely associated with intestinal epithelial cells. The data are discussed with respect to competition for nutrients and to the protection that some intestinal commensal E. coli strains might afford against infection by O157:H7 strains

Comparison of Carbon Nutrition for Pathogenic and Commensal ,\u3cem\u3eEscherichia coli\u3c/em\u3e Strains in the Mouse Intestine

The carbon sources that support the growth of pathogenic Escherichia coli O157:H7 in the mammalian intestine have not previously been investigated. In vivo, the pathogenic E. coli EDL933 grows primarily as single cells dispersed within the mucus layer that overlies the mouse cecal epithelium. We therefore compared the pathogenic strain and the commensal E. coli strain MG1655 modes of metabolism in vitro, using a mixture of the sugars known to be present in cecal mucus, and found that the two strains used the 13 sugars in a similar order and cometabolized as many as 9 sugars at a time. We conducted systematic mutation analyses of E. coli EDL933 and E. coli MG1655 by using lesions in the pathways used for catabolism of 13 mucus-derived sugars and five other compounds for which the corresponding bacterial gene system was induced in the transcriptome of cells grown on cecal mucus. Each of 18 catabolic mutants in both bacterial genetic backgrounds was fed to streptomycin-treated mice, together with the respective wild-type parent strain, and their colonization was monitored by fecal plate counts. None of the mutations corresponding to the five compounds not found in mucosal polysaccharides resulted in colonization defects. Based on the mutations that caused colonization defects, we determined that both E. coli EDL933 and E. coli MG1655 used arabinose, fucose, and N-acetylglucosamine in the intestine. In addition, E. coli EDL933 used galactose, hexuronates, mannose, and ribose, whereas E. coli MG1655 used gluconate and N-acetylneuraminic acid. The colonization defects of six catabolic lesions were found to be additive with E. coli EDL933 but not with E. coli MG1655. The data indicate that pathogenic E. coli EDL933 uses sugars that are not used by commensal E. coli MG1655 to colonize the mouse intestine. The results suggest a strategy whereby invading pathogens gain advantage by simultaneously consuming several sugars that may be available because they are not consumed by the commensal intestinal microbiota

Let us have articles betwixt us: Papers in Historical and Comparative Linguistics in Honour of Johanna L. Wood

Papers in Historical and Comparative Linguistics in Honour of Johanna L. Woo

Clinical emergence of neurometastatic merkel cell carcinoma: a surgical case series and literature review

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm of possible viral origin and is known for its aggressive behavior. The incidence of MCC has increased in the last 15 years. Merkel cell carcinoma has the potential to metastasize, but rarely involves the central nervous system. Herein, we report three consecutive surgical cases of MCC presenting at a single institution within 1 year. We used intracavitary BCNU wafers (Gliadel®) in two cases. Pathological features, including CK20 positivity, consistent with MCC, were present in all cases. We found 33 published cases of MCC with CNS involvement. We suggest that the incidence of neurometastatic MCC may be increasing, parallel to the increasing incidence of primary MCC. We propose a role for intracavitary BCNU wafers in the treatment of intra-axial neurometastatic MCC

A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development

Contemporaneous Observations of Direct and Raman Scattered O VI in Symbiotic Stars

Symbiotic stars are binary systems consisting of a hot star, typically a white dwarf, and a cool giant companion. The wind from the cool star is ionized by the radiation from the hot star, resulting in the characteristic combination of sharp nebular emission lines and stellar molecular absorption lines in the optical spectrum. Most of the emission lines are readily identifiable with common ions. However, two strong, broad emission lines at $\lambda\lambda$ 6825, 7082 defied identification with known atoms and ions. In 1989 Schmid made the case that these long unidentified emission lines resulted from the Raman scattering of the O VI resonance photons at $\lambda\lambda$ 1032, 1038 by neutral hydrogen. We present contemporaneous far-UV and optical observations of direct and Raman scattered O VI lines for nine symbiotic stars obtained with the Hopkins Ultraviolet Telescope (Astro-2) and various ground-based telescopes. The O VI emission lines are present in every instance in which the $\lambda\lambda$ 6825, 7082 lines are present in support of the Schmid Raman scattering model. We calculate scattering efficiencies and interpret the results in terms of the Raman models. Additionally, we measure the flux of the Fe II fluorescence line at $\lambda$1776, which is excited by the O VI line at $\lambda$1032, and calculate the first estimates of the conversion efficiencies of this process.Comment: 48 pages, 5 figure