Search

To the Editor: Frameshift neoantigen-based cancer prevention vaccines (e.g., Nous-209, NCT05078866) are being tested in clinical trials for patients with Lynch syndrome (LS) caused by monoallelic mismatch repair (MMR) gene [...]

The individual behaviors driven by information diffusion show an undeniable impact on the process of epidemic spreading and have been continuously evolving with the dynamic processes. In this paper, a novel weighted co-evolving multiplex network model is proposed to describe the interaction between information diffusion in online social networks and epidemic spreading in adaptive physical contact networks. Considering the difference in the connections between individuals, the heterogeneous rewiring rate, which is proportional to the strength of the connection, is introduced in our model. The simulation results show that the maximum infection scale decreases as the information acceptance probability grows, and the final infection decreases as the rewiring behaviors increase. Interestingly, an infection peak appears in our model due to the interaction between information diffusion and epidemic spread. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.09.030 Byline: Reginald Hill (1), Yurong Song (2), Robert D. Cardiff (3), Terry Van Dyke (2) Abstract: Our understanding of cancer has largely come from the analysis of aberrations within the tumor cell population. Yet it is increasingly clear that the tumor microenvironment can significantly influence tumorigenesis. For example, the mesenchyme can support the growth of tumorigenic epithelium. However, whether fibroblasts are subject to genetic/epigenetic changes as a result of selective pressures conferred by oncogenic stress in the epithelium has not been experimentally assessed. Recent analyses of some human carcinomas have shown tumor-suppressor gene mutations within the stroma, suggesting that the interplay among multiple cell types can select for aberrations nonautonomously during tumor progression. We demonstrate that this indeed occurs in a mouse model of prostate cancer where epithelial cell cycle disruption via cell-specific inhibition of pRb function induces a paracrine p53 response that suppresses fibroblast proliferation in associated stroma. This interaction imposes strong selective pressure yielding a highly proliferative mesenchyme that has undergone p53 loss. Author Affiliation: (1) Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA (2) Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA (3) Center for Comparative Medicine, University of California at Davis, Davis, CA 95616, USA Article History: Received 10 August 2005; Revised 6 September 2005; Accepted 20 September 2005 Article Note: (miscellaneous) Published: December 15, 2005

Recent advances in bone and calcium (Ca) metabolism have relied upon genetically modified mice. However, although human studies have identified gender as an important modulator of Ca metabolism, its effect on Ca metabolism has not been examined in mice. Here we examined basal and vitamin D-regulated Ca absorption (in situ ligated loops) and mRNA levels for the apical membrane calcium channel, TRPV6, and the calcium binding protein, calbindin [D.sub.9k] (CaBP) mRNA levels (real-time PCR) in duodenum of female and male mice. At 2 mo of age, females fed a 5 g Ca/kg diet had higher Ca absorption (62.3 [+ or -] 4.8 vs. 47 [+ or -] 3.6%) and TRPV6 mRNA levels than males even though plasma 1,25 dihydroxyvitamin D [1,25[(OH).sub.2] D] was not different. In mice fed high (20 g/kg), normal (5 g/kg), or low (0.2 g/kg) Ca diets for 7 d to alter plasma 1,25[(OH).sub.2] D (91 [+ or -] 12, 322 [+ or -] 25, and 587 [+ or -] 43 pmol/L, respectively), the relation between Ca absorption (slope = 0.116 vs. 0.084, P = 0.021) or duodenum TRPV6 mRNA (slope = 0.042 vs. 0.025, P = 0.034) and circulating 1,25[(OH).sub.2] D was steeper in females. After a single 1,25(O[H).sub.2] D injection (200 ng/100 g body weight), peak induction of TRPV6 mRNA was 2-fold greater (at 6 h) and CaBP mRNA was 20% higher in females (at 16 h). Duodenal vitamin D receptor mRNA levels did not differ between genders. Our data indicate that female mice are more sensitive to changes in serum 1,25[(OH).sub.2] D levels than males and that this must be considered when using mice to study calcium and bone biology. J. Nutr. 134: 1857-1861, 2004. KEY WORDS: * calcium absorption * calbindin [D.sub.9k], TRPV6 * gender * vitamin D

To study the role of calbindin [D.sub.9k] (CaBP) and epithelial calcium channel ECaC2 in intestinal calcium (Ca) absorption, vitamin D receptor knockout (KO) and wild-type (WT) mice were fed either 0.5% Ca or a 2.0% Ca rescue diet starting at 21 d of age. Ca absorption and parameters involved in this process were measured at 60 or 90 d of age. Compared with WT, KO mice fed the 0.5% Ca diet had higher plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]], and lower plasma Ca and insulin-like growth factor-I (IGF-I). Duodenal Ca absorption (% Ca absorbed) in KO mice was reduced 71% relative to WT mice and was associated with 55% lower CaBP mRNA, 47% lower CaBP protein and 95% lower ECaC2 mRNA levels. Compared with WT mice, the percentage of Ca absorbed in KO mice fed the 0.5% Ca diet was inappropriately low for the level of duodenal CaBP. The 2% Ca rescue diet normalized plasma Ca, prevented osteomalacia, increased growth and plasma IGF-I levels, but did not normalize plasma PTH or 1,25[(OH).sub.2][D.sub.3] in KO mice. In addition, the relationship between CaBP protein and the percentage of Ca absorbed was normalized, whereas ECaC2 mRNA fell to near zero. Our data demonstrate that higher CaBP levels do not ensure high rates of duodenal Ca absorption and that transcellular Ca absorption can occur even when ECaC2 gene expression is very low. In addition, our data suggest that the 2% Ca diet promotes a vitamin D receptor-independent anabolic effect on bone formation and calcium absorption, leading to improved calcium balance even in the presence of high PTH levels. KEY WORDS: * calbindin [D.sub.9k] * calcium channels * calcium absorption * bone * mice