Human Apolipoprotein B Transgenic Mice Generated with 207- and 145-Kilobase Pair Bacterial Artificial Chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine

We reported previously that ~80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We hypothesized that the absence of intestinal expression was due to the fact that these clones lacked a distant DNA element controlling intestinal expression. To test this possibility, transgenic mice were generated with 145- and 207-kb bacterial artificial chromosomes (BACs) that contained the human apoB gene and more extensive 5'- and 3'-flanking sequences. RNase protection, in situ hybridization, immunohistochemical, and genetic complementation studies revealed that the BAC transgenic mice manifested appropriate apoB gene expression in both the intestine and the liver, indicating that both BACs contained the distant intestinal element. To determine whether the regulatory element was located 5' or 3' to the apoB gene, transgenic mice were generated by co-microinjecting embryos with p158 and either the 5'- or 3'-sequences from the 145-kb BAC. Analysis of these mice indicated that the apoB gene's intestinal element is located 5' to the structural gene. Cumulatively, the transgenic mouse studies suggest that the intestinal element is located between -33 and -70 kb 5' to the apoB gene

SNPs in ultraconserved elements and familial breast cancer risk

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Are Italian medical societies bridging the distance from citizen and patients? associations? Results of a survey.

Introduction. In the framework of PartecipaSalute ? an Italian research project aimed to involve lay people, patients? associa- tions and scientific-medical representatives on the health debate ? we carried out a survey with the Italian Federation of Medical Societies. The aims of the survey were to know medical socie- ties attitude vs. patients involvement in research activities and healthcare setting and to find out possible projects conducted in partnership with patients associations. Results. A web-questionnaire with 17 closed questions, and three open questions has been prepared on the basis of some experiences published on the literature and through the col- laboration of members of the Italian Federation of Medical Societies. A total of 205 medical societies has been contacted by e-mail with a cover letter explaining the aims of the survey. At the end 74 medical societies completed the survey. Medical societies participating to the survey varied widely in terms of years of activity, number of members, and geographical distri- bution. Remarkably, 36 medical societies respondent organized collaborative initiatives with patients/consumers associations during the last three years. Among these, the most frequent were the preparation of written material for patients, organiza- tion of conferences or workshops, and health awareness cam- paigns. Moreover, 6 medical societies published documents on patients? rights but patients or their associations were involved in only 2 of these initiatives. Advantages and disadvantages reported by medical societies answering are also presented and discussed. Conclusions. In conclusion, to our knowledge this is the first survey on the value of patients? involvement conducted together with medical societies in Italy, and the results point the way to stronger collaboration in future between patients? associations and medical societies

TLR Activation Pathways in HIV-1-Exposed Seronegative Individuals

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Renormalization group in the infinite-dimensional turbulence: third-order results

The field theoretic renormalization group is applied to the stochastic Navier-Stokes equation with the stirring force correlator of the form k^(4-d-2\epsilon) in the d-dimensional space, in connection with the problem of construction of the 1/d expansion for the fully developed fluid turbulence beyond the scope of the standard epsilon expansion. It is shown that in the large-d limit the number of the Feynman diagrams for the Green function (linear response function) decreases drastically, and the technique of their analytical calculation is developed. The main ingredients of the renormalization group approach -- the renormalization constant, beta function and the ultraviolet correction exponent omega, are calculated to order epsilon^3 (three-loop approximation). The two-point velocity-velocity correlation function, the Kolmogorov constant C_K in the spectrum of turbulent energy and the inertial-range skewness factor S are calculated in the large-d limit to third order of the epsilon expansion. Surprisingly enough, our results for C_K are in a reasonable agreement with the existing experimental estimates.Comment: 30 pages with EPS figure