Patterns of DNA methylation in the normal colon vary by anatomical location,gender, and age

Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon’s normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays. We found that methylation levels of repetitive elements LINE-1 and SAT-α showed minimal variability throughout the colon in contrast to other loci. Promoter methylation of EVL was highest in the rectum and progressively lower in the proximal segments, whereas ESR1 methylation was higher in older individuals. Genome-wide methylation analysis of normal DNA revealed 8388, 82, and 93 differentially methylated loci that distinguished right from left colon, males from females, and older vs. younger individuals, respectively. Although variability in methylation between biopsies and among different colon segments was minimal for repetitive elements, analyses of specific cancer-related genes as well as a genome-wide methylation analysis demonstrated differential methylation based on colon location, individual age, and gender. These studies advance our knowledge regarding the variation of DNA methylation in the normal colon, a prerequisite for future studies aimed at understanding methylation differences indicative of a colon field effect.     

CCN proteins: A centralized communication network

The CCN family of proteins includes six members presently known as CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6. These proteins were originally designated CYR61, CTGF, NOV, and WISP-1, WISP-2, WISP-3. Although these proteins share a significant amount of structural features and a partial identity with other large families of regulatory proteins, they exhibit different biological functions. A critical examination of the progress made over the past two decades, since the first CCN proteins were discovered brings me to the conclusion that most of our present knowledge regarding the functions of these proteins was predicted very early after their discovery. In an effort to point out some of the gaps that prevent us to reach a comprehensive view of the functional interactions between CCN proteins, it is necessary to reconsider carefully data that was already published and put aside, either because the scientific community was not ready to accept them, or because they were not fitting with the « consensus » when they were published. This review article points to avenues that were not attracting the attention that they deserved. However, it is quite obvious that the six members of this unique family of tetra-modular proteins must act in concert, either simultaneously or sequentially, on the same sites or at different times in the life of living organisms. A better understanding of the spatio-temporal regulation of CCN proteins expression requires considering the family as such, not as a set of single proteins related only by their name. As proposed in this review, there is enough convincing pieces of evidence, at the present time, in favor of these proteins playing a role in the coordination of multiple signaling pathways, and constituting a Centralized Communication Network. Deciphering the hierarchy of regulatory circuits involved in this complex system is an important challenge for the near future. In this article, I would like to briefly review the concept of a CCN family of proteins and critically examine the progress made over the past 10 years in the understanding of their biological functions and involvement in both normal and pathological processes.     

不同水分处理下双接种丛枝菌根真菌和根瘤菌对疏叶骆驼刺生长及氮素转移的影响

以疏叶骆驼刺为研究对象,设定3个水分梯度正常水分(土壤相对含水量(70±5)%)、干旱胁迫(土壤相对含水量(20±5)%)和复水处理(干旱胁迫60天后恢复至正常水分)与四组接种处理(单接种丛枝菌根真菌(AMF)、单接种根瘤菌、双接种AMF+根瘤菌和不接种),分析不同水分条件下双接种丛枝菌根真菌和根瘤菌对疏叶骆驼刺的生长以及供、受体疏叶骆驼刺之间氮素转移的影响。结果表明,正常水分处理时,双接种疏叶骆驼刺的AMF侵染率、地上生物量、地下生物量、总生物量以及氮含量均要高于单接种处理;根瘤数量、最大荧光(Fm)、初始荧光(Fo)、最大光化学效率(Fv/Fm)与单接种处理之间无差异;在遭遇干旱胁迫时,双接种疏叶骆驼刺的AMF侵染率、总生物量、Fv/Fm均小于单接种处理;地上生物量、地下生物量、根瘤数、Fm、Fo以及氮含量与单接种之间无差异。复水后,双接种疏叶骆驼刺的地上生物量、地下生物量、总生物量、根瘤数均优于单接种;AMF侵染率、氮含量低于单接种;Fm、Fo、Fv/Fm均与单接种之间无差异。在氮素转移方面,正常水分时,双接种与单接种的氮素转移率无差异,在遭遇干旱胁迫时,双接种疏叶骆驼刺的氮素转...